Welcome to the 44th JP Morgan Healthcare Conference. I'm Richard Vosser, European Pharma Analyst at JP Morgan. It's my great pleasure to host the CEO of Novartis, Vasant Narasimhan, for this presentation. Just a housekeeping: if you have a question, you can either raise your hand or you can go through the portal, and with that, Vas, welcome to the conference.
Terrific. So very good. Happy New Year, everybody, and great to be here with you today. This is a momentous occasion because it's the first time in my tenure, entering my ninth year, that we are a buy rating from JP Morgan. So I'm really happy about that as I come here today. But overall, I think I'm really happy to share with you the story of where we are at Novartis on our journey. As you know, over the last decade, we've really focused as a pure-play medicines company, exited all of our businesses, focused on high-end leading technologies in the therapeutic areas we care about most. So just as a recap over the recent years, very strong sales, core operating income performance for the company 7% and 15%. That core operating margin by 2024 had reached 38.7%, on track to reach the 40% guidance that we had given.
I think this year, in 2025, we certainly have the opportunity to approach that 40% range, as you saw in quarter three. Now, I think importantly, what that strong performance has allowed us to do is generate very strong free cash flow. You can see the free cash flow generation for the company: $16 billion last year and $16 billion through the first three quarters of 2025. That's given us the ability to really turn around our return on invested capital. We're now at 17%. We're approaching the top quartile on return on invested capital amongst the peer set, showing that we have the financial firepower to stably fund our operations. And that's also being reflected now in the TSR for Novartis over the five-year period, in the top five in the industry, in the three-year period, top two in the industry. I think our strategy is working.
And importantly, it's returning tremendous value to our shareholders. Now, our strategy remains unchanged. We set this strategy out really five years ago. We think it's the right strategy. Once we've exited now the other businesses, four core therapeutic areas, the two plus three technology platforms, which I'll talk more about, our four priority geographies, and then our focus on driving growth and returns, strengthening our foundation. So a big focus on culture in Novartis remains to be the case: curious, inspired, unbossed company. And then continuing to deliver world-class operational excellence, as you've seen through that margin performance over the recent years. Now, our capital allocation priorities remain unchanged: invest in the organic business as needed, continue to do value-creating bolt-ons. You saw last year we were one of the most active companies from a BD&L and M&A standpoint.
We have the proposed acquisition of Avidity that we hope to close in the first quarter, acquisition of Tourmaline and Anthos, a number of licensing deals in our core therapeutic areas. We remain committed to consistently growing our dividend in Swiss francs as we have since the creation of Novartis and ongoing share buybacks. We continue to work to complete our $15 billion share buyback, which we initiated last year. We expect that to be ongoing through the course of this year, the $10 billion, excuse me, and then on an ongoing basis, we'll continue to look to additional share buybacks when we have excess capital. We see all of these components happening at the same time. It's not a sequence, and it's all with a view to return leading capital, leading value to our shareholders.
Now, taking a look at our pipeline, you can see that we've now developed, I think, one of the more deep pipelines in the industry. We don't face binary risk. We have 14 in-market blockbusters, which means that a single patent expiry, as you'll see this year with Entresto, we're able to grow through these difficult patent expiries when they happen. Nine in-market brands with multi-billion-dollar peak sales potential. I'll go through that in a moment. Six ongoing launches, 15 submission-enabling readouts in the next two years. So coming up on a real catalyst-rich period for the company. I mentioned the five platforms.
I did want to note that in those technology platforms where we're investing, we see markets here that are substantial: $36 billion for RNA therapeutics, $28 billion for radioligand therapies, and potential with the opportunity to reset immune systems up to $50 billion in cell and gene therapies. Now, turning to our long-term guidance, we guided to the markets in November: high single-digit growth 2024-2025, 5%-6% growth to 2030, and then mid-single-digit growth 2030 and beyond.
And what I hope to show in this chart is that's underpinned by a number of de-risked in-market brands that I think we'll talk about also with Richard, as well as a set of pipeline assets we think that we'll have the opportunity to launch in the coming years, and then a very deep portfolio of pipeline assets, as well as a number of brands that have protection into the mid-2030 period. That gives us, I think, that strong foundation as we continue to grow to $60 billion, $70 billion, hopefully in the middle of the next decade, approaching an $80 billion revenue company.
Now, when you look at our net sales growth in that period, it's going to be a story of offsetting GX, which we'll primarily face this year with the loss of Entresto, full-year effects of Entresto, Promacta, and Tasigna, in-market growth from our inline brands, and then that probabilized pipeline. Clearly, if the pipeline delivers in full, we have the opportunity to outperform that 5%-6%. But on a probabilized basis, we think this is a reasonable approach. I did want to note that as we've guided previously for 2026, we do expect 1%-2% of short-term margin dilution from the proposed acquisition of Avidity and then expect to get back to the 40% by 2029. We think we can get opportunities.
We have opportunities to get there sooner, but I think that's a reasonable guidance that it'll take us till 2029 to really absorb these recent acquisitions and then get back to the 40%+ where we'd like to stay. Now, when you look at our commercial execution, I think one of the things I've been extremely pleased about in the recent years has been outstanding commercial execution from both our U.S. and international regions, and here is an example from our U.S. business. You can see Cosentyx and Hidradenitis Suppurativa. Within month eight, we got to 67% in BRX share. When you look at Kisqali in early breast cancer, 63% early breast cancer share. Pluvicto, very strong performance. Importantly, Scemblix, very strong performance both in the first line and in the second line setting.
I think that shows now that we're a company that can consistently deliver, once we get an approval, the outlined launch trajectories, which we guide to all of you. That'll be, of course, extremely important as we now go through launches of Roxido, of Ianalumab, as well as other launches we have in the coming years. I also did want to note that from a geographic standpoint, we're number two in China, number one in Germany, number four in Japan with an aspiration to get top three in Japan. Our ability to balance geographically, I think, also is a unique value proposition that Novartis brings. Now, turning to peak sales guidance, these are some of the peak sales guidance that we outlined in November. As you can see, a number of brands with very significant potential.
I would take note that now we guide for Kisqali to be a $10 billion plus medicine. That's on the back of the very strong performance that we see in early breast cancer. Scemblix, we also now see with the long, strong trajectory that we have a $4 billion plus opportunity. We recently got the approval of Itivisma, which is our intrathecal version of Zolgensma, so for patients two years to 18 years with spinal muscular atrophy. We're guiding for that to be a multi-billion dollar medicine. And then very importantly for this year, one of our top priorities is the launch of Roxido, where we have the opportunity to have a multi-billion dollar medicine in CSU, as well as on many of the other indications that we'll be reading out over the next two years.
Now, when you look at our opportunity from a pipeline standpoint, you can see a broad pipeline here, and one asset I wanted to call out, a few assets I wanted to call out here, Ianalumab for Sjögren's disease, opportunity in Sjögren's to be multi-billion, but then across all indications, another multi-billion dollar opportunity. We're adding back on this chart Pelabresib. I'll show the data in a moment, but now with the very strong 96-week data that we have, this is an additional multi-billion dollar opportunity. We'll be filing in Europe and then with an additional study, hopefully filing in the U.S. Also we include here the Avidity assets as well as some of the other assets that we acquired over the course of last year, so over the coming period, we enter a real catalyst-rich period for the next two years.
You can see the number of readouts that we have on some of our key medicines. 2026 will be a very important year, important readouts that I think can underpin that growth into the mid-2030s, as well as in 2027, a continued regular flow of regulatory filings as well. So we'll be looking forward for these data readouts, keeping the markets up to speed. And then, of course, as we get those submissions in, the launch trajectory thereafter. Now, turning to Pelabresib, this was the data, 96-week data. We presented Pelabresib plus ruxolitinib. And the data showed at this time point, deep and durable responses with comparable safety to ruxolitinib. We presented this at ASH, very strong efficacy, significant reductions in spleen volume. You can see 91% versus 57%, twice as many patients reaching spleen volume reduction or the TS50 response, very good safety profile.
So now our path forward after a consultation with the EU will be to file this medicine in 2026 based on that 96-week data. We also have alignment now with the U.S. FDA to start a new phase three submission-enabling study, which will focus on patients with higher symptom burden at baseline, where we think we can meet the TSS 50 reduction based on the data we've seen here. So, new asset that we can add now to the portfolio, continuing our long legacy of treating MDS and CML and AML. And then when we look forward, the 30-plus high-value assets that we have in the portfolio, very excited both for the phase two and three assets, but also a number of phase one assets that we think can continue to show our replacement power, replace our sales, and drive growth.
I'll go through these in a little bit more detail on the pipeline-specific charts in a moment. I did want to note as well that from a BD&L standpoint, that over 10 of these assets have been licensed or acquired in the last two years. I think that shows how active we've been on the BD&L M&A front. Certainly at a conference like this, we want to continue to look for the best ideas that fit with our therapeutic area priorities, as well as our platform priorities to enable us to be successful in the long run.
Now, turning to each therapeutic area in turn, in cardiorenal and metabolic, I think an exciting portfolio that's underpinned both by our work in cardiovascular risk reduction on the back of Leqvio and Pelacarsen, trying to move further with siRNAs to more infrequently administered medicines, as well as a portfolio of assets in the renal space, which I think we were quite excited about as well. I would also say in the early phases of our research portfolio and early clinical portfolio, a number of assets targeting arrhythmia, which we think is a significant opportunity, high unmet need, difficult science, but if we're successful, can certainly help us with our long-term cardiovascular positioning, and seven phase 3 readouts in this portfolio between now and 2030. Now, three assets in particular I wanted to say a word about. First is abelacimab, which is our factor XI inhibitor for thrombosis.
You can see very good data that we had in AZALEA. This is a study that is now enrolling in phase III. We hope to get the readout over the course of this year or the early part of next year. It's an opportunity for us to tackle a very large patient segment. 50% of these patients don't reach their goal in terms of prevention of future events. So I think a really exciting program there. We also brought in an anti-IL-6 for reduction of inflammation residual risk in patients who are immediately post a cardiovascular event. Lastly, farabursen, our microRNA to tackle adult polycystic kidney disease, which gives us an opportunity to take on a relatively prevalent genetically driven disease of kidney disease, 160,000 patients in the U.S., an estimated 400,000-500,000 patients in our target markets, and with very promising phase 1b data.
And hopefully, if we had very strong efficacy in our phase two study, an opportunity to file off that data set. Now, turning to immunology, I've spoken a lot already about it, but clearly Remibrutinib is incredibly important now for the outlook of the company. We already have the approval in CSU. The CIndU readouts will happen in 2026. The opportunity to expand into hidradenitis. We had very good data in food allergies, so we'll also be taking it in food allergy. And then we also have a number of phase two programs as well to expand Remibrutinib over time. Ianalumab with the opportunity to clearly be a very significant medicine in lupus nephritis, SLE, on top of Sjögren's disease.
Then I'll say a word about YTB in a moment, because clearly our focus on being a leader in immune reset is one of the pillars for us in immunology in the long run. Just to say a word about that, T-Charge is our rapid CAR-T platform now, where we showed very compelling data in SLE in lupus nephritis last year on the first 24 patients treated. I think remarkable efficacy, where we really see across disease domains a return to normal biology for these patients, with the only residual impact being damage in the kidney that's already happened and difficult to reverse. We've entered now pivotal studies on a pretty broad range of indications, as you can see here.
We would expect readouts to start to happen in the 2027-2028 time period, alignment with FDA that those phase IIB readouts can be the basis of submission with confirmatory data to then support us longer term, and then earlier phase programs ongoing in areas like relapsing MS, primary progressive MS, myasthenia gravis, rheumatoid arthritis. So this is really a platform we plan to build out across the full gamut of severe immunological disease, and then also recently we've brought in a high affinity IL-15 monoclonal antibody that we're excited about. At least the early data would indicate to us this has a significant potential. This could be another pipeline and a drug opportunity for the company. We have an atopic dermatitis study ongoing, a number of other derm studies now in planning, so an opportunity for us to have a next important innovation in immunology.
Now, turning to neuroscience here, I think what I'm really pleased about is how we've built significantly more depth in our neuroscience pipeline and portfolio. As you know, we've been a leader in MS for a long time now, 20 years, and clearly on top of Kesimpta, we have the opportunity to life cycle manage Kesimpta to less frequent dosing, but Remibrutinib gives us the opportunity now with a clean liver profile, already established efficacy in CSU with the readouts coming, hopefully an opportunity to have another pillar medicine in MS. We're also studying Remibrutinib in myasthenia gravis and also bringing a taclopam as well into myasthenia gravis. Separate from that, a very, I think, broad portfolio, an exciting portfolio in neuromuscular disease. That's on the back of some of the recent acquisitions that I'll talk about as well, but certainly Kate Therapeutics, an opportunity to bring in gene therapies.
We have now the siRNA portfolio with Avidity, which we hope to close, as I mentioned, so an exciting opportunity there. And then lastly, neurodegenerative diseases. Now, just to say a word about the Avidity acquisition, this is a slide we showed immediately after the acquisition, but an opportunity to address three very high unmet need diseases with the first-in-class therapy for DM1, for FSHD, and for a subtype of DMD. Exciting data that I think will play out over the coming year or two. 80,000 patients with DM1, 45,000-80,000 patients plus with FSHD. And one of the things we expect is as we get drugs that ultimately can help these patients, diagnosis rates will likely increase as well. So the opportunity here could certainly be even larger than what we expect today.
And then lastly, turning to oncology, here our story is very much to build on the strength of Kisqali as well as our work with Pluvicto and prostate cancer. At the top of the chart, you can see the depth of the efforts that we have to ensure that we can continue our breast cancer leadership into the 2030s and beyond. Broad efforts in CDK2, CDK4, radioligand therapies, which I'll talk more about in a moment. Pluvicto as well, moving through its various indications, and then the opportunity to expand further within prostate cancer, both with Actinium as well as with oral agents. And then an ongoing effort to try to expand into cancers that are not well addressed. So this includes cancers like colorectal cancer, prostate cancer, cancers of the central nervous system.
That's something we want to continue to be aggressive about, because clearly we see the opportunity is to start to address those areas of high unmet need. Now, just to say a word of where we are on the radioligand therapy platform, you can see here the various targets at the top that we're currently pursuing in the clinic. So these are all in the clinic today. And the opportunity to address a broad range of cancers. So clearly prostate cancer, but neuroendocrine tumors, breast cancer, lung, PDAC. And then a number of efforts ongoing with undisclosed targets that we think have the opportunity to address multiple tumor types. So 16 programs now in the clinic, 22 preclinical RLT programs. We have both Lutetium-177 and Actinium-225 capacity now within the company.
We continue to believe, depending on the target, there is the opportunity to get a stronger therapeutic index versus antibody drug conjugates, and hopefully drive better efficacy over time with combinations. And as I've already mentioned, a $28 billion opportunity. So just a conference like JP Morgan, a conference like JP Morgan, important to recognize all the great innovation that's happened externally that we've been able to bring into the company through our efforts. So you can see here the full range of deals we've done in the last year. So very excited about that and want to keep that going in the year to come. And I wanted to close as well by just mentioning that our company continues to be a leader in ESG. We take this seriously. It's who we are as a company. ESG and global health are fundamental to what Novartis does.
You can see very strong rankings across the board, leadership index, and in many cases, both in our sector and across any sector. In global health, we've delivered last year two incredibly important breakthroughs, which matter a lot to me personally. Coartem Baby was launched in Ghana. I was there in Ghana for the launch. It's the first malaria treatment ever for children under five kg. Then we had the first phase three readout of a novel drug to treat malaria since our last readout of Coartem over 25 years ago. Another incredible breakthrough to be able to treat resistant malaria across the world. In closing, very strong results. You can see that the numbers, I think, speak for themselves. The growth profile remains attractive. We're confident in that 5-6% growth through 2030, the 40% core margin in 2029 and beyond.
And then lastly, the strong pipeline that we have and the 15 potential submission enabling readouts and the 30 potential high-value assets that we have to drive our growth in the long run. So with that, I'll move over to Richard. Thank you very much.
Thanks, Vance. Are there any questions in the room, first of all? I can't see any. Maybe please put your hand up if there are. So maybe first, sorry. Okay. First of all, maybe the 5%-6% CAGR, when the slide you put up seemed to suggest a large proportion of that would be realizable within market brands. So how should we think about the risk adjustment taken on the pipeline and the relative contributions there?
Yeah, I mean, I think when we look at it and we see the strength of the inline portfolio that we already have with big brands like Cosentyx over most of this period, but certainly Scemblix, Pluvicto, Kisqali, Leqvio as well, performing very well, so we have the opportunity with those, I think, to really have a strong foundation, and the pipeline really gives us the optionality to outperform, but when we look at the opportunities that we have, Remibrutinib's already in hand, Ianalumab already in hand. I think we just need one or two of the remainder to hit to have the opportunity to even beat that 6%.
Yeah, makes sense. Maybe on one of the in-line brands, Kisqali, you mentioned the 10 billion peak sales. We've seen data from the oral SERDs in this space. Maybe your thoughts on how all that impacts the 10 billion, if at all?
Yeah, I think when we look at it, it doesn't. First, it does not affect our outlook on the brand. I mean, we're very confident that Kisqali is on its own compelling proposition. And really our job now is to ensure we generate data with Kisqali with each of the relevant oral SERD. And we're doing that. We are pursuing agreements or plans to generate data with each of the competitor companies that have oral SERD, because we think the way the standard of care will evolve is that for the backbone endocrine therapy, an oral SERD will be an opportunity to do something other than the standard hormonal therapy that's used. And then you need to add a CDK4/6 on top. And a lot of that is going to depend on managing the safety profile.
So I think generating that data is our number one priority, but doesn't change our outlook for Kisqali.
Makes sense. You mentioned Ruxolitinib as well in hand, obviously just being launched. Maybe you could give us a little bit of color of the early stages, what the reaction has been.
Yeah, it's early days. And we wouldn't expect, I think, significant sales pickup until mid-2026. But I think the feedback from physicians has been very positive. So this is a medicine where we saw in the clinical studies resolution of or the beginning of resolution of symptoms in patients with hives or flares within two weeks. The anecdotal feedback we're getting is that within one or two days, many patients are seeing resolution of symptoms. And I think that in that context of patients who are highly symptomatic with a highly efficacious drug, we're seeing high demand from physicians in terms of patient start forms, many of the things that we track in order to give us confidence in the launch dynamic.
I would say in general, our experience is that when you have highly symptomatic diseases with high efficacy in a very short period of time, that's a strong recipe for a very strong launch, because we saw that, as you will remember, once we could actually get patients to understand the symptomatic benefit of Entresto, Entresto started flying. I think we have that kind of opportunity with Ruxolitinib.
And the other indications like CIndU, food allergy may be different, but are you seeing that same in your data, the speed of onset and resolution?
I think in these inflammatory conditions, certainly CIndU like CSU, we certainly see a very rapid impact. I think it'd be interesting to see with the MS data, of course, as well. It would be nice with hidradenitis because I think certainly the IL-17s with the TNFs and the IL-17s, there's a lot of efficacy still on the table for HS. I think either our drug or the competitor drug, this is not leading to significant improvements for these HS patients. So if remibrutinib could do that, then I mean, that's another $5 billion-plus market that this medicine could address. So really exciting.
And do you think of combos with Cosentyx there in terms of Ruxolitinib? Do you think that does make sense?
I think, as you know, in immunology, the hard part with combinations has always been stacking side effect profiles and things, and I think obviously with Cosentyx, life cycle where it is probably would be difficult. I think the good news with remibrutinib is thus far, as you know, we've seen no liver, we've seen no liver signals, very clean safety profile, so I think we're in a good spot.
Excellent. Maybe on RMS, we've not seen huge data outside of the company. What gives you the confidence in RMS? We've obviously seen mixed data from the competition here.
Yeah, I think we have to be humble here. I mean, I think we have to say that we haven't seen any data on our own. So I think we're basing our confidence off of what competitors have seen with their BTK inhibitors. Clearly, top line now from one of our competitors stating that they hit their endpoints both in PPMS and RMS. Certainly the data from another one of our competitors, a non-relapsing SPMS. So all of that would indicate the BTK inhibitors are active. I think now it remains to be seen how active and what the clinical data show, do you have the right safety profile. I mean, I think notable to me is what was said in the recent CRL from FDA, which I think points to how carefully FDA is looking at liver signals for these medicines.
We have a BTK inhibitor that's already licensed with a label that's clean on liver, and so that gives us a huge opportunity to differentiate if we can show the efficacy benefit.
Maybe a couple of. Oh, we have a few questions here at the front. I think maybe this gentleman here was first.
Vasant Narasimhan, first, congratulations for continuous efforts and ESG efforts front because malaria is an important effort for the population. My question is actually focused on oncology in terms of diversification in terms of modality. I think kudos to you. The RLT as a modality has now become a very important pillar in oncology. But on the other modalities, it didn't seem to be there's a lot in the portfolio. I would love to see your view on that.
Yeah, thank you for the question. So when we think about our oncology pipeline, we think about trying to ensure we have depth across small molecules, bispecifics, RLTs, and ADCs. Now, it doesn't always work out that we get there at the same time, but certainly our concept is to have compelling options in each one of those therapeutic areas. I would say right now a lot of depth in RLTs. The history of the company is very strong on small molecule drug design. So I think when you look at our ability to have a CDK2, CDK4/6, CDK4, two CDK4/6s. So we're really covering our bases on the small molecule side. I think two areas we're very interested in improving our depth are clearly bispecifics and ADCs where we don't have a compelling position. And that's something we're certainly looking at actively.
There's a gentleman with three over there, and then.
Hi, Vas. I'm Angus Liu from Fierce Pharma, also on oncology. So of course, Kisqali is doing well. But if we look at Novartis late-stage oncology pipeline, 15 plus submission enabling readouts and some of the phase three, phase two programs, there are a lot of excitement coming out of the oncology pipeline. Granted, this is from after NATALEE and PSMAfore, but is this, and last time I checked, I think you still don't have a permanent oncology R&D chief. So is this kind of you're taking a break from oncology late stage, or is there a plan to kind of fill that gap?
Is this an upcoming article, Angus?
Yeah.
So no, there's no break from oncology. We actually just brought in an incredible clinician, Mark Rutstein, who's in now to lead our oncology portfolio, outstanding PhD clinician scientist. So we have the right leadership team. When I think about it, often you have in therapeutic areas, these things come in waves. I mean, you have to remember we just had Scemblix, Pluvicto, and Kisqali, which combined could have $20 billion of peak sales. So now, before we declare big challenges for Novartis oncology, the fact that we were able to generate three drugs with $20 billion of peak sales is a reasonable outcome. And so I think we're in a period now where we need to reload.
I think some of the key things we'll have towards the end of the decade are readouts on a lot of the RLTs on the small molecule oncology pipeline and, as I mentioned, the bispecific portfolio. I do think we need to have more strength in oncology, there's no question. I mean, and that's going to be an active focus for us from a BD and M&A standpoint.
Hi, I'm Veenu Aishwarya with AUM LifeTech and AUM BioTech. We have an antisense platform for drug discovery. So being a small biotech in Philly, we are leveraging a lot of AI right now to advance drug discovery. I'm just curious to know your thoughts, someone like Novartis, which has all the resources in the world, how are you leveraging AI for drug discovery? And do you have any thoughts for smaller biotech so that we can advance drug discovery and development and partner up with you guys faster?
Yeah, I think AI is something that now has become part of the toolkit now for both target optimization, certainly for target identification, target optimization, I think candidate optimization. I'd say certainly from a drug target standpoint, we'll have to see how AI pans out. The way we think about it is having deep partnerships. So we have the partnership with Isomorphic Labs for the Google DeepMind team. We have the partnerships with companies like Schrödinger and GenerateBio. And those all just become standard toolkits for our biologists and medicinal chemists in terms of optimizing any candidates that we have. And so I think we're open.
I mean, to any partners who can come to us with good ideas on ways to enable this, because our vision would certainly be on average now from when you have a target that you want to prosecute with a drug to when we get it into the clinic, it's about four years on average in this industry. So how do you get it down to two? And how do you increase the probability of success of that effort significantly? Because as you know now, it's quite low. And then, of course, in the clinic, can we optimize trials, et cetera, is also high interest for us as well.
Your confidence in ianalumab and the potential seems to have grown even since the data in Sjögren's. So maybe you could just talk about what's leading to that increased confidence in Sjögren's and also the potential of the asset beyond.
You know, when you look at a disease like Sjögren's, the second most prevalent rheumatological disease without any real disease-modifying therapy available, and most of these patients, of course, are on high levels of corticosteroids, challenging quality of life, this is an opportunity, I think, to completely reshape a whole sector, so I think when we look at the data across NEPTUNUS I and II, when we look at the pooled data, there are important domains that matter to patients, things like salivary flow, things like lymph node size, where we see important benefits, and I think that's going to be very compelling, but I think the reality is a lot of the launch is going to be physicians trialing the drug, and they are going to begin to identify which patient profiles benefit most from ianalimab.
We'll learn as well then which patients to be targeting with our field force and our marketing efforts, and I'm confident there'll be a significant opportunity there, even if it's only 30%, 40% of that patient population just because of the sheer size of the patient population.
We've had a couple of questions from the web. So first one is on Zigakibart. So the person saying, "It's a disease-modifying therapy. Could this become a blockbuster asset?" Question.
Yeah, we think Zigakibart has a multi-billion-dollar potential. I mean, I think the challenge here is going to be in a setting where there's four agents coming forward, all with compelling proteinuria reduction, unclear eGFR benefit. How do you position it? The way we think about it is to focus very much now on eGFR. Proteinuria reduction looked very good. We also think from a safety standpoint, the fact that we target APRIL without BAFF, I think it could be ultimately a safety differentiator, but a lot of this will come down to the eGFR data and how robust that eGFR data is, and then your ability to use this in combination. I think the future of IgA nephropathy therapy is going to be combining in the appropriate way for the appropriate patient, a vascular agent, a complement agent, and an IgA targeting agent.
And figuring that out is now the ballgame. And the good news for us is we have all three. And hopefully, we'll get all three approved. And that will enable us to generate the data to help physicians navigate that.
On Fabhalta and Atrasentan, how are you seeing the uptake in IgAN?
So I think, as you saw already in quarter three, very solid uptake. I mean, I think these will be steady growers. Certainly with Fabhalta, we see that in PNH, C3G, now with IgAN, Atrasentan as well. I think what will be important as well for those two assets is the eGFR data. And I think we will be disclosing the eGFR data from Fabhalta soon. We should get Atrasentan data in the coming year. And I think that will give physicians even more confidence to ultimately prescribe these medicines. But so far, so good on the renal portfolio.
Makes sense. We've got another one from the web, which is on business development, and so they're just asking, in today's competitive biotech landscape, how do you position yourself within deals and your overall portfolio strategy in terms of risk diversification and value creation?
Yeah, I think we, of course, are always looking for opportunities that fit in our core therapeutic areas or fit with these technology platforms. I think what differentiates us, I'm sure every company thinks this, is you have to have deep scientific expertise that allows you to have a differentiated view on an asset. I mean, we have, I think, outstanding people expertise within neuromuscular disease, which allows us to build conviction to do a deal like Avidity, to do deals like Kate, DTX. If you actually look at the history, we've done now four deals across neuromuscular treating diseases with poor standard of care in neuromuscular disease. And that's based on real deep expertise. Similarly, in cardiovascular risk reduction, we've been at this a long time. We, of course, with the Canto study, understood that biology.
So then doing an IL-6 deal, doing deals like Anthos makes a lot of sense. So I mean, that's the recipe. There's nothing else to it. I think we tend not to be the company that wins the very aggressive auctions. But I think when we have a differentiated view, we'll go after it.
You mentioned, again, considering share buybacks. You obviously have significant R&D spend as well. Maybe you could talk about the free cash flow and the capital that allows you to do that so that you can not have to prioritize necessarily one thing over the other.
Yeah, I think for us, obviously, with the free cash flow where it is, approaching $20 billion, we're in a position, a very luxury position, that we're not capital constrained in terms of the deal sizes that we can look at. I think it's much more strategic fit, scientific fit. That's what has to really play out. Certainly, we also look at R&D expense. I mean, I think, of course, our R&D budget growing now, $11 billion, $12 billion over the coming period, significant R&D spend, and so, of course, you have to absorb the R&D spend, but certainly not capital constrained. It's really finding assets that make sense, which is why we've moved away from even providing target ranges in terms of the size of deals, and we want to do deals that make sense, and we have the capital to be able to do that.
You mentioned upfront the 100-200 basis points of margin contraction around Avidity and around Entresto, well, this year. What's encompassed in that beyond? We've had a lot of sort of healthcare reform. There's IRA, all sorts of things going on.
Yeah, all of our guidance already takes into account the recent agreement we signed with the administration on most favored nation. And that's primarily driven by the Medicaid component and then, of course, the impact on XUS launches. But that's certainly all factored in. We also factor in the fact that we assume IRA inclusion of Cosentyx and Kisqali in 2028. Now, importantly for that, interestingly, given that both Cosentyx and Kisqali, certainly in the EBC setting, is not a very Medicare-oriented population, but the spillover effect into Medicaid and 340B is where you see the effects. And I think it's always important for investors to look at spillover on best price whenever you're looking at IRA pricing. But that's all factored into the guidance. And so that gives us, I think, a high degree of confidence now looking ahead.
Makes sense. Makes sense. Maybe a last question just to return to one of the growth drivers. Pluvicto, you've got new indication. We'll then see a new indication, the addition study, maybe this year as well. How do we think about the cadence of adding those new indications to boosting sales?
Yeah, as you saw with Vision, then we had PSMA IV. Now we're on a strong trajectory. We upped our guidance there on Pluvicto, very confident in that $5 billion plus outlook for that medicine. And I think with PSMA addition now, we'll see that next opportunity. And probably after that, getting into the earlier stages, oligometastatic prostate cancer will take a bit longer. But in the meantime, we're going into pivotal studies as well, or I already started the pivotal studies with the Actinium-225 PSMA. I think more important even than the Pluvicto performance is we believe now we've established RLT in the community setting in the United States, which was an incredibly important unlock. It was a two-to-three-year effort. I give tremendous thanks to our U.S. team and working so hard at that.
But now we have over 700 centers that are able to prescribe RLT and growing. We have figured out those patient pathways. And what that opens up is for the whole future pipeline of RLTs at Novartis, we have the ability to launch these medicines at scale. And that took time with Pluvicto. It shouldn't take as long for the next wave of positive readouts.
Perfect. I think we're out of time, unfortunately. Thanks very much, Vasant.
Thank you very much, Richard.
Cheers. Good to see you.