All right. Hello, everyone, and welcome to our 2025 Meet Novartis Management Investor event. Thank you, as always, for your time, interest, and engagement with us. This is a special event, which we've been doing for over 10 years because it allows investors and analysts to interact with our management teams in an open Q&A format. Today, we'll start with a presentation and a Q&A by Vas, followed by breakout sessions with our core therapeutic areas and corporate. The breakout sessions will be in a different room, so I'll come back after Vas's presentation to give directions and help you get where you need to be. One other quick housekeeping note: for the Q&A after Vas's presentation, we'll have mic runners in the room. Please wait for the mic before asking your question so that we can ensure our webcast audience hears you clearly.
Before we get started, I'll just read the Safe Harbor Statement. 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 20F on file with the U.S. Securities and Exchange Commission for a description of some of these factors. The discussion today is not the solicitation of a proxy nor an offer of any kind with respect to the securities of Avidity Biosciences or SpinCo. The parties intend to file 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. With that, I'll hand it over to Vas.
Thank you, Sloane. Let me also thank everybody for joining today. It's always a pleasure to have all of you come in and be able to interact with our management team. I think one of the things that's allowed Novartis to perform so well for so long is that we believe we have the best talent in the world, and that that talent will be here today, and you'll have the opportunity to interact with our leaders in R&D and the commercial space to understand more about why we have such conviction for the long-term growth of the company. Let's start with a little bit of history, and I think we've been trying to update this chart each year.
As you know, as we've focused as a pure-play medicines company with the exiting of and the successful spinoffs of Alcon, Sandoz exiting the consumer health stake, the sale of the Roche stake as well, we've been able to drive very strong performance over the year: 7% sales growth, 15% core operating income growth, 1,100 basis points of margin improvement. I think this demonstrates that our pivot to a focused strategy focused on four key therapeutic areas, focused on key geographies, is paying off. Now, when you look at some of the financial implications of that focus, first, looking at free cash flow, you can see that in the first nine months of the year, the cash generation machine of Novartis is really functioning in a powerful way.
You can see that $15.9 billion already comparable to the 2024 full year number, and that allows us to invest in the business, allows us to invest for growth in the long run. The other element of the story is, with the focusing of the company, we continue to see improvements on return on invested capital, which now is at 17%, which is above peer median. That has been a focus area for us to really demonstrate that in the long run, we're generating return on the capital that we deploy. Now, looking at how does that translate as well into total shareholder returns? On the five-year period, Novartis is in the top five in the sector, and in the three-year period, number two in the sector, again demonstrating that all of that focused financial performance is also translating into returns for our shareholders.
This is something, of course, we want to continue to deliver now in the period to come. Now, from a strategy standpoint, there is no change. I think one of the things that we've seen since we did transforming for growth, exiting the businesses that I mentioned, having a consistent strategy that focuses on key therapeutic areas, on technology platforms that we'll describe and talk about a bit more that you all know well, four key geographies, and keeping that consistent with a ruthless focus on generating growth and returns, having strong foundations, including in data science, technology, and artificial intelligence, which I'll talk more about, continuing to be a leader in ESG topics, which I'll also briefly mention later on, and then continuing to drive productivity, which is why we've been able to see the strong margin performance that we've seen over the recent years.
Our commitment is to continue to maintain this strategy with consistency and strong execution in the years to come. From a capital allocation standpoint, no changes, but just to go over again so that we're really grounded on how we think about capital allocation. First and foremost, we need to invest in the business, and we need to make sure that our capital, CapEx and R&D infrastructure and capabilities are well invested in. We focus on value-creating bolt-ons without a size. I know there's a lot of focus on how big are the acquisitions. We really think about, is it an acquisition that can generate strong financial returns for the company? Does it fit with our key therapeutic areas and technology areas? And is it something that we think can generate growth over this 10-year period?
Some of the examples, as you know well, the proposed acquisition of Avidity, we did Tourmaline, we did Anthos. If you look at the overall frame of the recent years, 30 deals over the last year, which was by, I think, most measures, number one in the industry, showing that we're deploying capital to bring in technology and new medicines. We have the commitment for a consistent growing dividend in Swiss francs. The other thing we've demonstrated is we're prepared to do share buybacks on an ongoing basis to continue to return capital that we're not deploying in the other three areas to shareholders. Right now, we have the $10 billion buyback ongoing. We're prepared at the next appropriate time when this share buyback is completed to continue share buybacks if we have excess capital available.
Now, I wanted to turn for a moment to the portfolio and just to give you a little bit of an overview of what we're seeing right now and the shape of the portfolio. I think a couple of interesting things to note here. One, 14 in-market blockbusters, eight in-market brands with $3 billion-plus peak sale potential, and limited binary risk. 16% of our sales comes from our largest product. Now, on top of that, six ongoing launches. Part of what gives us confidence in the growth outlook that we outlined this morning is 15-plus submission-enabling readouts and 30 high-value pipeline assets, which you'll have the opportunity to discuss with our teams over the course of today. Now, we continue to focus on key platforms.
We spend a lot of time talking about the three newer platforms, but I would say we continue to invest in capabilities, in chemistry, in biotherapeutics. I mean, these are areas that have to be the foundation of any company. Of course, that technology is also moving as well as we get into novel formats in those molecules. Now, we estimate that in the three newer areas where Novartis is building a leadership position: $36 billion market in RNA therapeutics, $28 billion market in radioligand therapies, and by some estimates, a vastly growing cell and gene market to up to $49 billion. Now, we've also had a big focus on R&D productivity with the shift to a pure-play medicines company. You'll remember in 2022, we did a significant pruning of the portfolio to focus down and ensure we're only really looking at high-value assets that are on strategy.
What that's led to is a 50% increase in our portfolio in terms of median peak sales value per project, as well as an increase of 25% in the ENPV on a per-project basis. Also, we've been working on cycle time, something where we have not been, I think, where we would like to be in the top quartile of cycle time, so a big area of focus for us in the company. We've now accelerated first patient to first site initiation visit by over 40% in 2025 versus 2024. When you look at last patient, last visit to CSR, getting a series of clinical study report, again, accelerated by over 15%. Concrete examples of that included with Scemblix, where in first line, we were able to get to approval in three years from the start of the study.
With Unalimab, we were actually able to get enrollment to be completed nine months faster. We see examples like this across our portfolio. Now, turning to the growth outlook of the company, as you saw in our announcement this morning, first, just as a reminder, as part of the Avidity acquisition, we upgraded our guidance for 2024-2029 to 6% sales growth. In the 2025 to 2030 period, we guided this morning to 5-6%. The 5-6% to indicate that we're roughly in the midpoint of that range, and we'll continue to see how this will evolve over the pipeline readouts that we have upcoming. Our expectation is to continue to deliver mid-single-digit sales growth into the 2030s and beyond.
Now, what underpins that is de-risked in-market brands, which you all know well, and we'll talk about a little bit more, but as well as a growing number of pipeline assets that we think can underpin the longer-term growth of the company. I would also say that many of those key assets on the top part of this chart have LOE protection well into the 2030s, into the late 2030s. That gives us a strong base from which we can grow in that period. In a little bit more detail and to make it super clear, 5-6% constant currency growth. Now, on the core margin, we did speak about with the Avidity acquisition. We do expect one to two percentage points of core margin decline in 2026 with the Avidity acquisition, and then a climb back up to the 40% plus by 2029.
We, of course, will have productivity programs in place to try to get that to happen sooner, but we think this is a reasonable guidance to give us the opportunity to invest in those Avidity assets, invest in the pipeline to ensure the long-term growth outlook that we're aspiring towards. Now, to look at the trajectory of this over the coming period, I think there's been a lot of focus on the GX that we have with Entresto, Promacta, and Sysigna, and that will certainly have a significant impact on us in the first half of next year. Coming out of the midpoint of next year, we would expect to enter a period where we have limited generic headwinds, and then we have a lot of tailwinds that will enable us to drive the dynamic growth that we're forecasting.
That's in-market growth drivers that we'll talk about on the next few slides, and then a probabilized pipeline that, as we see more and more readouts with Ianalumab, with some of the other medicines that we have here that we'll have readouts in the next two years, will give us the opportunity to hopefully outperform the guidance that we're giving you. Now, I would want to say, I do want to highlight that we've become very effective now at consistently launching our medicines. If you look at the history, certainly I've been at the company for more than 20 years, we historically have had a lot of variability in launch performance.
We've had a significant focus now on trying to ensure that we execute each launch successfully, knowing how important that is to actually unlock the value for the company, but also have the impact that we want on patients and the healthcare system. When you look at this chart, you see out to month eight from launch, the performance of four recent launches in the U.S. market. You can see with Cosentyx HS, we were able to achieve 67% NBRX share. In Kisqali, early breast cancer, with a very strong competitor in the market, 63% NBRX share. PSMAfore, we're at 16% NBRX share in four months. With Scemblix as well, 56% in the second line and 23% in the first line. Very strong launch performance, and that's something we're really going to focus on, continue to focus on in the years to come.
I would also say outside of the U.S., where we have a history of being one of the market leaders in most key markets, that same commitment to launch excellence is also being implemented. You can see with China, we're now the number two in the market, Germany number one, and a very nicely growing business in Japan, where we see significant opportunity in the years to come, up to number four with the aspiration to get into the top three. Now, turning to the peak sales guidance that we outlined as well this morning, we had eight, as I mentioned, eight in-market assets with $3 billion-$10 billion of peak sales potential.
Based on the strong performance we're seeing in the early breast cancer setting in the U.S., but importantly also outside of the U.S. in the early readings that we're getting, we're upgrading Kisqali to $10 billion plus peak sales potential, which would make it really Novartis' largest brand in our history. We maintain our outlook on Cosentyx at $8 billion, underpinned as well by the recent positive readout we had in polymyalgia rheumatica. We're maintaining our Kesimpta outlook at $6 billion plus. We certainly see very strong momentum on Kesimpta, but we think overall that's prudent given the competitive dynamics and also our own Remibrutinib's potential as a BTK inhibitor in MS. We will continue to revisit that as we see the outlook for some of those brands become more clear.
Pluvicto, we're guiding to $5 billion plus, certainly a potential to become a larger brand, but we would like to see now the uptake as we continue to see the maturation in the PSMA4 population, as well as the PSMA addition readout approval and looking at the uptake there. That will give us a better sense by next year as to how big this brand can get. We're upgrading Scemblix now based on the strong brand share growth that we're seeing that I outlined on the previous slide. That's both U.S., but also outside of the United States. In some of our key markets, even in the face of generics available in the first line setting from first and second generation TKIs, we still see very strong uptake and interest in the physician and patient community, which gives us the confidence to raise that Scemblix guidance. Leqvio, Fabhalta, we maintain.
With Rapsido now, we provide, I think, a little more clarity on the outlook for this brand. We're very excited about this medicine. You have a medicine here with a very clean label, very fast onset of action, symptomatic disease, high interest from allergists and dermatologists. We're guiding the multi-billion dollar potential in CSU. Separate from that, a multi-billion dollar potential in the additional indications where we expect readouts in the years to come: chronic inducible urticaria, food allergy, hidradenitis, and multiple sclerosis. Now, turning to the pipeline, we are just giving some guidance here on what we expect to see from some of these pipeline assets. This includes some of the more new assets that we've brought into the portfolio. These all have significant potential, as you can see on the chart.
Probably some of the things I'd want to highlight is we do believe that OAV101 intrathecal, which is Zolgensma intrathecal, where we expect approval in the U.S. before the end of the year, as well as European approval next year. The opportunity to be a multi-billion dollar medicine, very strong data here that probably has not been fully understood, and so we think that's a significant opportunity. With Ianalumab's positive readout in Sjogren's disease, we think a significant opportunity in Sjogren's standalone, but then also in the additional indications across immunology and hematology, a significant opportunity. Both of the assets that we hope to acquire in our proposed acquisition of Avidity, Deldesiran, and Delbrax with a significant potential.
Faraburson, which is the microRNA that we've acquired for adult polycystic kidney disease, a disease that has no standard of care, a relatively severe renal condition, we believe has the opportunity to launch within this period with a significant peak sales potential. And then some of the other medicines at the bottom, as you know well, Pelacarsen, Avalastramab, as I've already outlined for stroke, and then as well our IL-6 inhibitor for cardiovascular risk reduction also acquired via the Tourmaline acquisition. Here is the catalyst path. We do enter a period where we would think we have 15 potentially submission-enabling readouts in the next two years, a catalyst-rich period of time. Some of the readouts in 2026, you can see highlighted here. We'll provide more transparency on first half or second half at full year earnings, as we always do.
We think this is a pretty exciting time now to demonstrate that these medicines will have the potential to drive that growth 2031, 2032, and beyond. I did also want to highlight, because this is a great opportunity in this meeting, to understand better the early stage portfolio. We have 30 potential high-potential medicines in our pipeline. These are all MMEs, both phase one and phase two, three. I think what's interesting versus last year is that there's an opportunity to learn a lot more about this portfolio when you look at the number of assets that we've brought into this chart versus last year.
Along with the Avidity acquisition, we also have other medicines, siRNA medicines like QCZ, the HTT Huntington's medicine you know well, as well as in the right-hand side of the chart, some additional additions, IL-15 antibodies, as well as some of the additional prostate cancer assets we've brought on board. I think there's an opportunity to get a better sense of the pipeline depth we're continuing to build by investing in the portfolio. I just wanted to take a moment and go through each of the therapeutic areas. Again, you'll have the opportunity to dive much deeper with the teams. In cardiovascular, I think some of the key things now that we're working towards delivering, first with Lecvio and, of course, seeing the readouts now for other PCSK9 inhibitors, gives us a lot of excitement now to get to the readouts in secondary and primary prevention.
We would expect in secondary prevention, the two ongoing phase three outcomes trials to read out in early 2027. There we have, I think, the potential to demonstrate with the long follow-up we have that Lecvio has best-in-class cardiovascular risk reduction. The opportunity with the primary prevention is to set hopefully a similar or better standard for those patients as well. Strong uptake we're seeing for the medicine, particularly outside the United States. We think with China potentially having an NRDL listing for Lecvio, the opportunity for significant volumes for this medicine. Pelacarsen, which I've already mentioned, as well with Avalastramab, the opportunity with a monoclonal antibody, which we think has very good ability to knock down the target versus the orals.
The opportunity here to hopefully have a medicine for patients that are ineligible for the DOACs, and I think an opportunity there, particularly as we see how the oral data unfolds. We also are advancing our LTP001, which is our SMURF1 inhibitor in a proof of concept study. The idea here is, can we come up with a better profile versus the established medicines for pulmonary arterial hypertension? Some of the other highlights I mentioned, the IL-6, where given our expertise in inflammasome and inflammation, having done the CAMTOS study, the concept here was to bring in this IL-6 medicine monthly, sorry, Q3 monthly dosing. I'll talk about that in a moment. It is something we're really excited about. The renal portfolio continues to advance as well.
We can talk more about over the course of the day how we see the potential of having Atracentin, Eptacopan, and Zigotybard having three different mechanisms in Eigan, and how we see that as an opportunity to bring kind of an integrated solution to nephrologists. Now, just in a little bit more detail, so with Avalastramab, I think all of you know well, atrial fibrillation with a significant cause of comorbidity and death. Now, I think what's maybe less well understood is 55% of patients treated with the indicated doses of DOACs have a bleeding risk that remains, and that rate is 12-16% over two years, showing that there is a substantial market opportunity for patients who are ineligible or not responding to DOACs. There was very good phase two data with the Azalea study.
It was stopped early given the bleed reduction that the study saw versus Rivaroxaban. That phase three study is enrolling with AF patients or enrolled, readout expected in 2026 for AF patients unsuitable for DOACs. We think an exciting opportunity. Now, with the anti-IL-6 inhibitor, as I mentioned, we know well that this is a residual inflammation remains a key risk factor for cardiovascular risk reduction. It is an independent predictor, but I think what we've also understood better is that the patient group that will benefit most is actually patients who are post a recent event where the inflammation is more elevated and there's an opportunity to hopefully have a better impact.
For this medicine, which we acquired with Q3 month dosing versus the competitor medicine, this monthly dose, the phase two Tranquility study showed a significant reduction in HSCRP, which of course would be the marker here. In patients that we can identify post event with elevated HSCRP, can we knock it down and reduce the risk? We also believe there's elements of study design we can leverage here. That's a phase three asset study preparation for a phase three study in 2026. Lastly, the Faraburson, the microRNA I mentioned, potentially first in class microRNA, promising phase two B data for biomarker impact in slowing disease progression in patients with adult polycystic kidney disease.
This also would have a phase three start in 2026, but I also think important phase one data that we're working to generate, which could hopefully show the impact we could have for these patients. Now, turning to immunology, I think a lot of the focus of today should be on Rapsido and the opportunity that we see here advancing across the whole portfolio. With Unalimab as well, building off of the positive Sjogren's data, we have readouts now expected in lupus nephritis and SLE, as well as in systemic sclerosis in 2027. I'll cover the hematology readouts in a moment. There is a very broad program in YTB, which we'll talk about in the next slide. The atopic dermatitis work we're doing is where we really set a high bar.
I mean, our goal would be to set a better standard of care than Dupixent, a very high bar given how good a medicine that is, but something that we continue to evaluate. Now, just to say a word about T-Charge, which is our YTB CART therapy for immune reset in patients with B-cell driven autoimmune disease. We see this as a pipeline in a drug. You can see here all of the various indications now that we're pursuing for this medicine, but in particular, I would highlight the immunology indications. On top of the data we've already presented on SLE and lupus nephritis, ongoing pivotal studies in systemic sclerosis, idiopathic inflammatory myopathy, ANCA associated vasculitis, and then as well, earlier stage studies in RA, two forms of multiple sclerosis, myasthenia gravis, and Sjogren's disease. A very broad portfolio now we're taking forward.
We do have alignment with FDA on the pivotal requirements. We can talk more about that for the indications. As we get more data on the earlier stage, we would want to, of course, use that understanding for the first set of indications to hopefully advance those medicines forward. The other medicine that we're increasingly excited about, though it's still early, is GIA 632, which is our high affinity IL-15 monoclonal. IL-15 is overexpressed in atopic dermatitis, as well as a number of other diseases. We see this as a pipeline and a drug potential, so we're taking it forward in three different indications already with the hope to generate proof of concept data and then rapidly expand. Some of those pivotal, those POC studies, I should say, are starting up later this year.
From a neuroscience perspective, we continue to have a strong focus, of course, on MS. We have the Kesimpta Q2 month dosing program with a readout in 2027, which will allow us to lifecycle manage Kesimpta. Importantly as well with Remibrutinib in MS and myasthenia gravis, readouts are expected in 2026 and 2028. We have now initiated for Remibrutinib a progressive MS study, which is now recruiting. Part of that is focus on secondary progressive MS, but our neuroscience team can also outline how we're thinking about primary progressive as well. As I noted, T-Charge continues to be a very important part of our longer-term goal of getting these patients closer to a full remission from their disease. Separate from that, a big effort now in neuromuscular disease. I think it's one of the important areas we've really built out in the company.
Building off of the success we've had with Zolgensma, we'll be launching, as I noted, OAV101. We also have EDK060 as well for Charcot-Marie-Tooth syndrome. This is a disease. This is a lipid conjugated siRNA that we acquired, something we're recruiting. This trial is recruiting, and again, no standard of care. I think in some of these diseases like Charcot-Marie-Tooth, adult polycystic kidney disease, if we're able to demonstrate compelling data in early phase studies, certainly our aspiration would be to see how can we get this to patients even more quickly.
With our gene therapy work that we have brought into the portfolio with Kate Therapeutics as a longer-term follow-on, this would, of course, be in the mid-2030s. The idea would be building off of the work that we have with the proposed acquisition of Avidity, continuing to have a solution for patients that might be interested in a gene therapy for diseases like FSHD and DMD. At the bottom, of course, the Avidity Project portfolio. Separate from that, in neurodegeneration, continued work in ALS, Huntington's disease, and Alzheimer's disease with different mechanisms that we think are highly attractive. You will remember from the presentation that we gave a few weeks ago on Avidity, we see significant market potential for both Deldesiran and Delbrax.
Both have the potential to launch in this upcoming period, Deldesiran in the phase three study with a readout expected in 2026. That has, I think, very good phase two data, which we hopefully will be able to replicate in the phase three study and a significant market potential with no standard of care, disease-modifying standard of care for these patients. Separate from that, the ongoing phase three for Delbrax in FSHD, with the potential, high risk, but certainly a potential for an accelerated approval with the CDUX4 biomarker readout expected in mid-2026 as well.
Then lastly, the ongoing expected filing for Delzoda in a smaller population of DMD patients, which we believe really de-risked this platform by showing very compelling data that the drug hits the target, it improves the muscle biomarkers, and I think very compelling data to show that this antibody conjugated siRNA technology does what's expected. Lastly, turning to oncology, a broad portfolio with a big focus on breast cancer and prostate cancer. In breast cancer, of course, now with the oral SIR data, I think will be high on people's minds. I am just thinking an opportunity to discuss that with our oncology team.
We do have ongoing trials with partner companies to generate data with Kisqali in oral SIRs so that if physicians want the partner agent to Kisqali not to be current endocrine therapy, but actually one of the oral SIRs being developed, that that data is available and that Kisqali can be used with any of the choices a physician might make, as well as our goal to generate data with Kisqali and immune selective PI3K kinase inhibitors. There is also a significant effort in CDK2, CDK4. We have ECI830 in phase one studies, as well as CDK2, 4, and CDK4 agents also advancing preclinical into the clinic. Lastly, our RLT portfolio, we have Neobombicin, as well as FXX489, which is our FAP RLT, as well as HER2 RLTs as well now advancing for the treatment of breast cancer.
In prostate cancer, building off of the portfolio we have in Pluvicto, both mCRPC and HSPC, we are advancing now, I think quite rapidly, the actinium portfolio for Pluvicto. PSMA-617, which is the actinium using the same ligand as Pluvicto today, that is advancing now in phase three studies, always in the post-Pluvicto setting, but in multiple settings. We also have the R2 second gen, which we continue to evaluate, which is a different PSMA targeting ligand to evaluate if we can get a better safety and efficacy profile. We have invested to bring on board through three deals, additional small molecule agents, which could be partners with RLT or also just complement the RLT portfolio. That includes the AR degrader partnership, EZH12, which we brought in through the MorphoSys acquisition, as well as AMA 0959, which is in DNA damage repair.
Beyond prostate and breast cancer, we continue our efforts in a number of other cancer oncology tumor types. You can see here at the bottom a number of those programs that you're happy to get into. I think one of the ways to outline the breadth of our effort in RLT is with this chart, where you can see at the top we've outlined the current targets that we've disclosed within our RLT portfolio, the different cancer types, and how we're thinking about applying RLT to target as many cancers as we think is relevant, where we think we can get the right therapeutic index and have a high efficacy result for patients. You can see that nicely demonstrated here, as well as I think a number of undisclosed targets, undisclosed tumor types we're also pursuing.
We currently have 16 clinical and 22 preclinical RLT programs demonstrating, I think, the size of this effort. We continue to work, as I noted, beyond Lutathera to also bring Actinium on board. Our goal is on any target that we're pursuing where there's already ADCs available to demonstrate a better overall profile, so better efficacy with a lower side effect profile. We continue to explore combinations, as I noted, and a very large market potential for RLTs. Now, just to take a look at that 30 deal portfolio, which I've mentioned, we have, you can see here a number of deals, the number of deals we've conducted phase three and phase two, but I wanted to note a significant number of deals in an exploratory preclinical space.
That is with our goal to ensure we're covering key technology areas, areas where we think we can have a differentiated approach or build leadership in. You can see a high degree of activity, but also in the bottom of this chart, a significant amount of activity in partners who can work across our therapeutic areas and also build up our machine learning and artificial intelligence capability. That is something we'd like to continue as well to maintain a steady flow of bringing in a technology into Novartis. Just to give a little more color on that cross-portfolio impact, this outlines the work that we're doing in each step of the process in R&D and all the way through launch with various technologies, artificial intelligence, and machine learning with a whole range of partners at the bottom.
We are happy to discuss this, but I think some of the areas where we have seen significant progress is in chemistry with our Gen Chem and biologics optimization with partners like Generate Medicine, Schrodinger, and Isomorphic Labs. We have discussed in the past our large-scale partnership with Palantir to ensure that we have Data42, which allows our scientists to work, look at data across this whole spectrum of data that we are generating. Some of the areas we are now focused on much more is in the launch space, can we actually get much more efficient with using the substantial investments we make in marketing and launch preparedness. I do want to say a word about our manufacturing footprint as well, where we continue to aspire to primarily be internalized in manufacturing.
As I said, we're also primarily internalized in R&D, with the thought being that in areas where Novartis will be for decades, we need to own the capability and build world-class expertise and then deploy technology so we capture the value creation by getting more and more efficient. We also want to be the leader in these advanced technology platforms. With the portfolio of sites that we've built out, we now have a global footprint for radioligand therapies using both automated and semi-automated lines, which give us the ability to deliver 99.9% on time in full. In markets that we launch our RLTs, we're now at that 99.9% rate, which creates, we believe, a very strong protection for this business because it's very hard to replicate that kind of expertise and delivery times.
Similarly, when you look at XRNA, so this is our RNA therapeutics, some of the largest sites in the world in terms of volume in producing RNA therapeutics. That's primarily in Switzerland and Austria with a plan to add a site as well in the U.S. Substantial cell and gene footprint as well, so the ability to deliver the YTB platform and future CART therapy platforms in immunology, as well as continuing to have our small molecule and biologics presence. Now, yesterday we did announce as well, jumped ahead, we did announce as well an expansion in our U.S. footprint. We've already announced a number of sites around the country, but last week we announced the expansion in California of an RLT site. We'll be adding a site in Texas and Florida that would give us five RLT sites.
That enables us to reach any patient and physician that needs an RLT within a road. We can actually use road transport or captive supply chain to actually get it to the patient on time. We have announced this expansion in North Carolina yesterday, which will allow us to have our biologics production and small molecules production as well in the US for the US. That will allow us, I think, to mitigate various risks, including tariff risks in the future. We are quite excited about that, and that expansion is now underway. I do want to close with also noting that Novartis has continued to be, I think, really the leader in our sector and one of the leaders across sectors on material ESG matters.
Number one in the Access to Medicines Index, now a AAA MSCI rating, low risk on Sustainalytics, we are A level on CDP, climate, and water. Even though we know that these things come and go in terms of focus for various investor groups, we stay the course because we believe this is just the right thing to do, right thing to do for our company, right thing to do for our impact on the world. We will stay the course on this front regardless of how the winds might move. I did want to note with great pride some of the breakthroughs that we're delivering in global health. The Coartem Baby, I attended the launch in Ghana. This is the first ever malaria treatment specifically designed for infants two to five kilograms.
Last week we announced a positive phase three readout for Kafnoquin, so that's KAF156, a medicine I've personally been working on for a decade. That's a next-generation malaria treatment and the first novel innovation in malaria since 1999. I think that demonstrates the impact we can have on public health and the world. In closing, strategy is delivering a 7% sales growth, strong core operating income and margin performance, strong cash flow generation, leading an attractive growth profile given all of the uncertainties and risks in the current environment, 6% sales growth through 2029, 5-6% from 2025 to 2030, underpinned by a strong portfolio, on track for that 40% core margin after the dip we expect next year, and then a robust pipeline with strong capabilities, the 15 submission-enabling readouts and 30 potential high-value pipeline assets.
Thank you again for being here for a full day. We appreciate all of your time and commitment to learning about the company and your investment in the company. I'll close here and take it to questions. I see a few hands. I'll start with Sachin. I think please wait for the mic and I'll just try to move across the room.
Hi there, Sachin James, Bank of America. Thanks for the questions. Two on products you've mentioned on peaks with some debate, so perhaps a bit more color. Kisqali, you referenced the SIR data, so why don't you just give your perspectives? It sounds like you're thinking about this as a combination product rather than head-to-head competitor versus Natalie.
On Kesimpta, again, just a bit more detail as to how you think about BTK positioning versus CD20 and your differentiation of Remibrutinib versus Fenebrutinib. Thanks.
Yeah, thanks, Sachin. I think first on the SIR, of course we have to see the data set. I think it's important we understand the full data set. As you know, there's been mixed data thus far across the industry with oral SIRs and the ESR1 mutant population versus the Alzheimer's population. I think important to look at that data set. In our view, when we already have a situation where 55% of early breast cancer patients are receiving CDK4/6 inhibitors of one type or another, that shows that this is already a well-established standard of care, also with the various guidelines around the world. In our view, for most physicians, this will be how do you combine these agents rather than not provide a CDK4/6, given that our CDK4/6 studies were all done on optimized endocrine therapy.
I think that's how we currently view it, and we'll have to see how the data unfolds. Now, with respect to Kesimpta, again, we have one study out of five that has hit, and I think we need to understand better that data and see the second study for the competitor, also look at our own data. I would still expect that BTK inhibition will be difficult. It would be difficult for an oral drug to demonstrate the kind of impact that anti-monoclonal antibodies have on B-cell depletion. Rather, this could be an option for patients who either do not want an injectable therapy or as a therapy for patients who maybe have progressed on monoclonal antibody-based therapy. Again, this will all be data-driven.
When we think about our Rapsido Remibrutinib profile, I would note that we have a clean label, so we don't have liver as a warning and precaution in the label. It's something that we think is manageable for us given the data set that we have. Given that, we've been able to go high on the dose, so 100 milligrams b.i.d., where we think we have strong target engagement. We have a high degree of specificity on the target, as well as covalent binding. I would note as well, we also are neuropenetrant based on the data that we have in-house. Taken together, we think that gives us a very good profile. I'll go to Simon and then I'll come to this side of the room. Simon?
Thank you. Simon Lake from Redburn. Two if I may, please. Doubtless today we're going to talk an awful lot about the U.S. market because of its considerable importance. What about Europe? It's 30% of your sales. While sentiment is clearly improving and the government's behavior in the U.S. is definitely improving, it feels like it's going the other way in Europe. Thoughts on where Europe's going, particularly in an MFN world where pricing over there is going to affect pricing over here. Secondly, you touched on commercial execution and launching and lessons learned. I just wondered if you could go into a bit more detail and give us some examples there, particularly as they apply to ianalumab coming up in Sjogren's and potentially pelacarsen in cardiovascular. Thanks so much.
Yeah, thanks, Simon. I think overall Europe, Europe is at a kind of pivotal moment right now, especially in the large European markets. I think with the MFN agreements, the five agreements already signed, it's clearly making it clear that European governments have to rethink how they value medicines, both in terms of the initial prices, but as well as the various clawbacks and other mechanisms that exist to suppress, I think, growth in the European setting. I don't think that's going to be a fast process, but I think this whole situation is going to have to lead, is going to lead to a rethink. We see that already with some of the governments that we meet with, but it won't be a fast one.
I think in the interim, what you're going to find is that there will be classes of products that will be only launched in the private market in Europe in the context of the MFN negotiations. I don't think that'll be all medicines. There'll be some medicines that can be managed, some countries that can be managed given how these calculations are done, some classes that will continue to be launched globally. In those eight countries that are in part of this calculation, there will be a shift. I think if you take a medium-term view, our hope is that this leads to a reset in how medicines are valued, and then Europe can become a much more attractive market over time. In the meantime, I would note as well, though, that Asia continues to become a significant opportunity.
China, Japan, also the rest of Asia with high growth rates. You are seeing a shift, I think, to an Asia, increase in the Asian impact on our sector. The second part of the question was.
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Oh, the launches. I think on the launch side, there is some, I think, very bold things that we've done that maybe are underappreciated. Under the leadership of Victor and Rashima, both of whom are here, we reorganized how our US organization is launched. I mean, we actually are not set up in the US the same way as many of our peers. We functionalized and created functional expertise in areas like market access, and our market access leaders here, Rob Rubinsky, market access in marketing, in field force, in analytics, in patient support. We have the product teams more as integrated teams. That allowed us to build very deep functional expertise, kind of like what we do in R&D as a normal course of business.
The concept there was, given how fast things are moving, you can no longer have silos of therapeutic areas. You actually have to bring all of the learnings you have, let's say, in market access and payer negotiation across all your therapeutic areas. That gets you faster access, that gets you deeper access, that hopefully gets you lower gross to nets, and then you get more fast uptake on the products. That is the thinking that we put in place in the U.S. I really believe that's now paying off when you see the consistent launch performance. Richard, oh, sorry, Matthew has some things. Richard came into view first.
Thanks, Sas. Maybe just to pick up on Sachin's question, just Rapsido, you reiterated sort of the guidance, but there's a lot of excitement from you here on that one. What do you need to see to give us a number there and how big can you think that could be? Maybe just on the guidance, you've given a range for the first time. What is the major product or area that can get you from the bottom to the top?
Yeah, thanks, Richard. First on Rapsido, it's still early days, but the very early signals that we see in terms of patient start forms and interest from the physician community, particularly allergists, is very strong. I think that gives us confidence that starting next year, when we also start to see paid scripts come through, that that will give us some momentum. What we'll be looking for is access. When do we get the full access and how much access do we get at which time points? Of course, the pull-through on the scripts in those first two quarters of next year. That will give us, I think, a good sense of how fast this ramp is going to happen.
That said, I mean, in terms of the outlook for this brand, everything that we had thought of having a medicine, oral, safe, fast onset, highly symptomatic disease, standard of cares, all injectables that take 12 to 16 weeks to have their impact, the excitement is clearly there. It seems to be in the market. We expect that in the U.S., but also in ex-U.S. as well. That was on Rapsido and.
The five to six.
The five to six. On the opportunities here for upside, we'll all come from the pipeline. I mean, look, I think we're going to be watching carefully those readouts that you saw. I think clearly if the readouts come earlier, certainly for the proposed acquisition of Avidity, that will give us, I mean, I think a significant upside overall on the outlook. We currently outlook to 2028, those approvals. If they come earlier, I mean, that's going to lead to a significant ramp. Certainly, we've probabilized pelacarsen. We've probabilized avalastramab. We've probabilized the anti-IL6 as well as the other indications for Remibrutinib and Ianalumab. As those unprobabilize and we see positive readouts, I think that would give us more confidence to get to the 6% or higher. Matthew.
Thanks, Sas. It's Matthew Weston from UBS. Two questions, please. The first on the guidance range. One of the moving parts in 2030 is Cosentyx, LOE, and biosimilar entry. Can you just tell us, are you assuming, let's call it a normal biosimilar erosion in 2030 in your assumptions, or is there something extra that means you think you can extend Cosentyx? The second question is around ianalumab, because that's one of the areas where you as Novartis are clearly excited. The market arguably is quite skeptical. If I look at that April BRAF market, there are lots of players in there. Some of them are looking at rare disease and then coming like IgAN and coming down into Sjogren's and other areas. You are really positioned more as, let's call it mainstream for ianalumab. What does that mean for pricing?
Should we think Cosentyx pricing, or should we actually think that there's somewhere like an immunology premium price and that would help us get to your numbers?
Yeah. On Cosentyx, our current assumption in this is the biosimilar entry date, which we've always guided to, so first half of 2029. We continue to pursue alternative additional approaches to protect the full patent estate, IP estate that we have for Cosentyx, but that would be all upsides to the forecast. That's the base that we've assumed. I think the biosimilar erosion curve is also similar to the ones that we've seen. We've taken into account as well the shifting regulations now we have in biosimilars, where certainly from an efficacy standpoint, FDA looks to be becoming much more flexible, like the Europeans on that front. I think for ianalumab, as always, we don't comment on pricing until we get approval. Our overall thinking, one, is we do have differentiated presentations from oncology and the hematology indications and the immunology indications.
That gives us ability to price differentiate across those two indication sets. I think certainly our overall focus for this brand is very much these larger indications, Sjogren's, SLE, lupus nephritis. I mean, part of our excitement here is you do not have on-label medicines available for these patients other than high-dose corticosteroids. You have the opportunity here with a medicine for those physicians that might be using all sorts of B-cell inhibitors that are not on-label. Now they move on to an on-label therapy, which from a reimbursement standpoint, I think is going to be much easier for the patient and easier for them. For those 40-50% of Sjogren's patients, we think this is going to be something that will be tried. We will find patient groups that have significant benefit. There will be some that also do not benefit.
That will be something that physicians are going to be willing to do given the lack of meaningful alternatives. You can just give it to Steve. The mic went away. Steve. We can just keep the mic here. I think it's going to be. In the back, I'll get to the back as well.
Thank you very much, Steve Scaller from TD Cowen. Two questions. First on Kesimpta. Last year at this meeting, you noted lower expectations for potential competitors as one reason to raise numbers 50%. This year, you're using competitors as a reason not to raise guidance. In the last year, what we've learned is that the competitors have toxicity issues, at least the BTKs. Ocrevus SubQ has rolled out slowly. Remember, remibrutinib being in phase three doesn't strike me as a real plausible reason. I'm wondering what's behind this. Like, what are you really concerned about? Secondly, and this is following up on Matthew's question, but I'm a bit surprised that 2025 through 2030 sales growth is not even higher. The patent expirations are partially impacting the base, whereas that was not the case last year.
I appreciate Cosentyx patent expiration in 2029 with the emphasis on plus and the decay post-LOE probably should not be dramatic. Novartis seems to have a strategy to sustain Cosentyx, which it does not elaborate on. Why is not the growth higher? Thank you.
Yeah. Yeah, I think on the first question on Kesimpta, the reason we feel even more confident versus last year is the strong performance we're seeing in the market. When we look at this brand, it's growing steadily around the world and growing in a really attractive way. Now, why not go even higher with the toxicities and other things? I think there's a few things. One, there is a ceiling here on the MS market. I mean, there is the fact that you have very large drugs like Kesimpta and Ocrevus, and the patients here are not unlimited. It's a pretty well-penetrated class of market. There is kind of a ceiling effect that we're hitting here in just the number of patients.
If you want to go higher than $6 billion, you have to believe we are going to take significantly more share than we outlook versus the IV therapies. I think that's something we have to get more comfortable with. I mean, we've been pretty steady on our NBRX share and total share in the U.S., and we're benefiting from the growth of the B-cell class. Again, you can make a more aggressive assumption on how much more will the B-cell class replace braces and older therapies. If you make that assumption, you can get to a bigger number for sure. We take, I think, a more conservative view given we're already at 65-70%. The question is, will that get any higher? If it got higher and we see that trend continuing, certainly the brand has upside potential.
I think on the 25-30, I mean, the one thing you didn't mention that we, of course, have to factor in is the IRA negotiations that will happen on Kisqali in particular, but also on Cosentyx. I think for the 2030 period, notably, Kisqali will have an IRA. We would expect an IRA impact in that period of time, right? You had 2028. Important to note as well, whenever you think about IRA, it's not just the Medicare segment. It's also the spillover into best price. Certainly on Kisqali, this is a brand without that, we believe would become even larger. With that, that is something that does create a constraint on the system.
I think in terms of being more aggressive out to 2030, I think some of that will come from just seeing these upcoming launch trajectories and pipeline readouts. Certainly, we have the potential to be more than that 6%, but we would want to see, I think, more evidence before we go higher. Maybe James right behind you, and then I'll come over to Michael.
Thank you, James. Good evening, Goldman Sachs. Two questions, please. First on China, what have you assumed in the guidance, or what does the guidance broadly assume for China growth, and how are you assessing the opportunities and risks in the region, particularly as we discussed last night in terms of patent hacks? Secondly, on M&A and business development, how are you thinking about the need here? You showed on the slide 13 of your 30 high-value pipeline assets, so around 40% come from external innovation. We've done 30 deals in recent years. Should we expect this to slow down? Do you have enough in the platforms you've acquired to keep you going in the midterm, or should we expect the same pace? You made an interesting comment about deal size. I think this time last year it was up to $5 billion.
Avidity was obviously above that, but how are you thinking about deal size and shifting valuations?
Yes, I'm going to also just speed up a bit here because the clock is ticking down. On China, we've historically seen a business here that's grown well over 20%. This year, we had a significant slowdown with some of the shifts in the environment there, particularly pullback in spend in the government, but also increased competition on some of our brands, particularly Cosentyx. We expect our China business to get back to the low teens kind of growth range and that 10%+ growth range. That's what we're aspiring to. We do expect the market to recover. We do think we'll settle down to a position where we can manage these competitive entries, though it's something we have to get very smart about. I think there's a lot of very effective activity now happening in Shanghai.
From a deal standpoint, I don't think we want to do the same number of deals as we did because we need to kind of metabolize the deals that we've already done, which is quite a bit. We do want to have a focus on deals that we think can add growth. Again, size is not a constraint. I think at this point it's just more how much can we absorb, given that we did Tourmaline, we did Anthos, we did Avidity, we've done the 30 deals. I would actually think a little bit of a slowing down on the pace for the first part of next year, and then we can speed up again after that. Michael? First go to Michael and see how many more in a minute and 40 seconds. How many questions can I do?
I'll be quick. Thank you. It's Michael from Jefferies. Just on going back to the geographic split for us, I think for a few years now you've been saying the U.S. needs to be more of a focus, but I think your geographic split of revenues is still unusual compared to peers. Is that okay just because the portfolio performs so well outside the U.S., or is there a focus to drive that split? On siRNA, on the slides you say multiple assets going into the clinic soon. Does that include obesity?
Obesity, yeah. In terms of the profile, actually, when we look at the five-year period, we should probably get to about 55% sales US by 2030. We are going to see a shift. I think that's probably a healthy balance because we do think of ourselves, one of the strengths of Novartis is we globalize innovation. We are arguably the most global biopharma company. Even with all of the ups and downs of MFN, I don't think we want to change the long-run potential of Novartis always to take the medicine and go global and have very strong positions in the markets that we participate in. I think that's the thinking, but we will see a shift. We expect to be seventh or eighth by 2030.
I think if the Avidity assets hit, we could even be in the top five in that period of time. The second one was siRNA. Yeah, so the siRNA in the portfolio we have there, there's not obesity. A lot of that focus is longer-acting cardiovascular risk reduction, which is a big focus area, so longer-acting renal agents. That is very much where we're spending the energy. Obesity-wise, earlier stage, you can talk to Sean Coughlin about it, much more looking at novel mechanisms or novel formats to address some of the unmet needs by the first and second-generation therapy. I'll do Florent, and then we'll stop.
Good morning, Florent Cespedes from Bernstein. Two quick questions. First, a follow-up on the guidance. If you sign a deal with the Trump administration, how confident are you to be in a position to reiterate your top-line guidance? My second question, more a mid-stage pipeline question. On the slide 18, there is a list of assets in phase two and phase three. Could you maybe share with us which are the most exciting ones? The usual question. Some assets will compete in pretty areas where you will be a lot of competition, such as atopic dermatitis or prostate cancer or areas with unmet medical need, but still graveyards, such as Alzheimer. Maybe could you share with us how confident are you to be in a position to differentiate your assets? Thank you.
I've mainly focused on the first part of the question there. We feel confident based on our understanding with the discussions we're having with the administration that we'll be able to absorb those discussions in our guidance. We don't expect that to shift the guidance that we're giving you today. It's been incorporated. I would say on the assets, I think you could ask the team on the ones they're most excited about. What I see is a balance between diseases that have no standard of care or limited standard of care, where we have the opportunity with things like the Avidity deal or with polycystic kidney disease amongst others to create a whole new standard of care for these patients. That's one group.
There is another group where we have very strong positions like prostate cancer, breast cancer, and immunology, atopic dermatitis, where we want to see can we continue those franchises in the long run. Hence, we pursue those technologies and therapies even in the face of competition, but with the idea that we have a very high bar and we need to cross it. With that, I will hand it over to Sloane to give us some logistics and look forward to having more discussion over the course of the day. Thank you.