Good afternoon, everybody. My name is Karen King. I'm the Global Head of Investor Relations, and I'm sharing the stage today with my IR colleague, Laurent de Weck, which many of you speak to on a daily basis. So a couple of things. I want to introduce my team first. Just I want to thank them also for all the hard work that goes into planning an event like this. But Tamara Hackl, if you can kind of wave, Tamara. Tamara does a lot of our corporate governance. She does a lot of our ESG. She also does our IR website. And then Katie Fisher at the back of the room. Katie probably, you know, probably welcomed you when you came to this meeting. She probably sent you the invitation. She also does a lot of our conferences and our road shows.
We really appreciate you being here today and choosing to spend the afternoon with us. You know, we're about a year out from spin, so we thought this would be a great time to connect with you. We have a robust set of presentations we hope you will find both insightful and educational. And then just on a logistical note, if you need anything throughout the course of the day, if you have any questions, you can contact anybody from Sandoz. We're all wearing white lanyards. So this is the disclaimer. I'm going to read a little bit of it for you. Today's presentations and discussions include forward-looking statements. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events and are subject to significant known and unknown risks and uncertainties.
Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. The presentations also include non-IFRS financial measures, as defined by Sandoz, and an explanation of those can be found in the supplementary financial information in our Half Year Report 2024. All the presentations have been posted on the website, so if you go to investors.sandoz.com, you can find them. They're under Events and Presentations. Also, the webcast for today will be available at the end of the day. Objectives for today, they're really simple. We have five objectives. We want to reiterate our strategy and talk about our progress to date. We believe we've made a ton of progress over the past year, and we want to share that with you.
The second is we want to highlight key initiatives behind our midterm ambitions. We are not changing those ambitions. We set them last year at the Capital Markets Day, and we're just going to talk about our confidence behind those. Then, you ask a lot of questions around the U.S., so we are going to deep dive into the U.S. business, talk about our biosimilar framework. We also get a lot of questions about our pipeline, what's coming next, what's kind of longer term. So we're going to talk about some of that. What are some of the new technologies? And then the last one here is really spend time with management. We have some fantastic leaders here today. Some of them you've probably met, some you haven't met. So introduce yourselves. We'll have time at the breaks.
We'll have time after we finish up here as well. So with that, I'm going to turn it over to Laurent.
Thank you, Karen, and good afternoon, everyone. So let's start with the agenda. So we have divided the afternoon in two main session. The first session will focus on a strategic update and our path forward to 2028. Richard will summarize the key achievements to date and how they set us up for long-term success. Then Remco will focus on the midterm plan, including the progression made to date and key ongoing initiatives. This session will be followed by a 20 minutes Q&A session and a 15-minute break. The second session will focus on the U.S. market and our pipeline. Keren will deep dive on the U.S. market and how we want to position ourselves. Then, at the end, Rebecca and Claire will close the day by highlighting the significant opportunities remaining ahead of us and how we are best positioned to create value.
We will have a final 30 minutes Q&A at the end of the second session, where you will be able to ask questions to all of our presenters. And also, we want to encourage you to go to our product booth, that you maybe saw when you entered the room today, to really see the product we have, we have outlined there. And we have two internal experts, Monica and Rolf, who are really happy to answer any of your questions and give you information on these products. So today, we are very happy to have 5 incredible members of our management team presenting. Many of them have spent decades working in healthcare, and they all bring a tremendous amount of experience to Sandoz. First, we have Richard Saynor, our Chief Executive Officer.
I think all of you, all of you know him. He has been nearly thirty years in the generics industry and leads Sandoz since twenty nineteen. He has been instrumental to bringing the company to independence. Second, we have Remco Steenbergen, who joined us on the first of July, as our Chief Financial Officer. Remco was previously CFO at Lufthansa, and if you recall, he was also serving as one of our board member, which gave him insight on our business and strategy. Third, Keren Haruvi, our President, North America. Keren has over twenty years of experience in pharmaceuticals and leads the North American region since joining Sandoz in 2021 . And fourth, Rebecca Guntern, who you might have previously met as President of Europe. She just recently, on Monday, started a new role as Chief Commercial Officer.
She has over twenty-five years of experience in the pharmaceutical industry and is at Sandoz since nearly seventeen years. And finally, Claire D'Abreu-Hayling, our Chief Scientific Officer. Claire has over thirty years of experience in healthcare and joined Sandoz in 2021 . With that, I want to hand it over to Richard for the first presentation of today.
Good afternoon. First of all, thank you so much for coming today. Thirty years, I clearly started the industry when I was a child. Thank you all. Thank you so much, Laurent. Thank you, Keren. It's a real pleasure to be here. I'm pleased to be in Zurich. I mean, can't believe it's nearly a, well, just over a year since we had our first Capital Market Days in New York and in London. And as Keren mentioned, I'm gonna update you today on our strategy, which is very much consistent to what we presented last year. I'd also like to talk about our progress over the year and highlight some of the exciting opportunities that we see going forward.
I'm also, as Laurent introduced, excited to have some of my management team here with me, who will also deep dive into some of the topics that I intend to introduce. Our board, management team, employees, all share a common passion for our purpose. Everything we do is ultimately geared to pioneering access to patients, and we do that by having a deep generics and biosimilars portfolio and offering more affordable medicines to patients where and when they need them. Sandoz is a generics and biosimilar industry leader, and with top positions in many of the markets that we serve. The off-patent medicines market in which we operate provides about 80% of global medicines at approximately 25% of the total cost. Because we offer more affordable medicines and expand patient access, we make a huge social impact.
Today, we provide about 800 million patient treatments per year and generate annual healthcare savings of about $18 billion in the U.S. and Europe alone. The total social impact of our medicines, measured by direct health benefits to patients, as well as the benefit of a healthier population to the economy, is estimated to be around $400 billion a year. This impact, backed by a long track record of supplying high-quality medicines, is the foundation of our business success. We are also committed to our ESG goals and being a forward-looking leader in the industry. We are fortunate to have a built-in social purpose of expanding access for patients in our strategy, and we're also committed to our planet, and we'll follow a stringent carbon reduction plan in line with the Paris Agreement goals.
Sandoz is positioned to create sustainable market leadership and long-term value creation for our stakeholders. The brand Sandoz is unique with respect to its strong heritage in the Swiss market and globally, and this comes from the trust that we've built over the years with regulators, customers, patients, and partners by creating deep and broad pipelines, delivering high-quality products that are important to the medical community and to our patients, and having the voice to positively transform our industry. Let's remember, we were the first company to launch oral penicillin back in nineteen fifty-one, and more importantly, the first company to launch the first biosimilar back in two thousand and six, which is still today growing strongly. We are a European champion and have strong local relationships across nearly forty markets, which allows us to take a leading share position, even if we were late to market.
Our product portfolio is deep in therapy areas such as immunology and oncology. So when we do launch new products, we can leverage our existing infrastructure, and this is why many companies increasingly choose to partner with us. Our international business has consistently grown over the years, aligned with our targeted competing approach, and our U.S. business is turning the corner, which I know Keren will proudly talk to you more shortly. You'll see this slide consistently across all the presentations today, as we're going to take you on a journey, starting from with where we are today and what we've accomplished since then, reiterating the midterm goals that we laid out for you at last year's Capital Markets Day, and reinforcing our pathway to deliver on these aspirations, and then lastly discussing our future.
How are we planning to win some of the vast opportunities that we have beyond 2028 to ensure a sustainable leadership position? Let's start with the market. We play in a large and growing market of nearly $200 billion, which is expected to grow at about a 7% compounded growth rate over the next ten years. I will remind you, this is based on gross sales and not net sales of which we report. We generate sales of over $9 billion, with approximately a quarter of our revenues coming from our biosimilar business. Biosimilars have contributed strongly to growth in the recent quarters and was the primary driver for our 7% growth that we delivered in the first half of this year.
And as I discussed earlier, we are a European champion with a presence in over 40 markets and a leading position in the vast majority. We are the only company in Europe with a balanced portfolio of both biologics and small molecules. This, addressing the needs of our customers, healthcare providers, and healthcare systems. When you look at our pipeline, it is strong and diverse, with over 450 generic products and 25 biosimilars. You'll see throughout the day that generics will remain a key driver of growth in the long term, with the largest generic opportunities in the next decade being the GLP-1s, which we will discuss further through today. There's also a significant opportunity in the biosimilar business, both in the near term and in the longer term....
We have ultimately a strong balance sheet, which gives us the flexibility to support our near-term investments in IT, R&D, and in manufacturing. Generics are a large part of our business, and in many ways are synergistic with our biosimilars in development, medical, regulatory, and commercial. Having an infrastructure in both gives us the scale and the platform in hospitals and clinics to introduce our products. As you can see from this pie chart, our current generic portfolio has significant presence in many of the therapeutic areas, including cardiovascular and oncology. When we launch a new oncology biosimilar, we are leveraging this presence, as the oncologist ultimately doesn't distinguish between a small and a large molecule as they think about their patient. Our generic business is also extremely cash accretive and gives us the platform to invest in our higher value-add products, such as complex generics and biosimilars.
We have made significant progress with our biosimilar business, and since spin, every product we have submitted for approval has been approved, and the vast majority of those that have been approved have now been launched or have an upcoming launch date. We are gaining share, and we're currently the number one biosimilar provider on a worldwide basis in Europe and in our international regions. And we have a rapidly strengthening position in North America with the recent launch of Hyrimoz. In the next two years, we will add to that Tyruko, Pyzchiva, Jubbonti, and Enzeevu, which is an incredibly exciting opportunity. When you look at the split of our business by region, roughly half our business comes from Europe, but about 50% of the top-line contribution in the midterm will come now from North America. Each region has slightly different characteristics and strategies.
If we start with Europe, as I mentioned previously, we're very much a European company at heart, and we're investing in our pipeline with a very much a European lens. In Europe, every single biosimilar we've developed, we filed. Every one we filed, we've launched, and every one we've launched, we've ended up in a leadership position. We have a significant commercial infrastructure built on our strong customer relationships, which allows us now to continue and leverage. Then, the U.S. becomes a much more accretive opportunity on top. In the U.S., our goal is to become the number one biosimilar player. We are launching three major products in the next year and leveraging areas which we have a significant presence. This will also create a mix shift and contribution to our midterm margin goals.
In the US generics, our aspiration is not to be a number one, but to be selective in the choices that we make and to leverage our global portfolio. And again, Keren will talk more about this shortly. Our international business is growing strongly, with more than 80% of our sales in select markets where we have a direct presence and targeted M&A to complement the existing portfolio. As I mentioned previously, generics and biosimilars have many synergies. However, they have very different costs of development and life cycle curves. Small molecules or standard generics take about two to three years to develop and cost $1 million-$2 million. The cost often settles around 80-90% of the originator. Biosimilars, on the other hand, can take anything between six and nine years and cost anything between $100 million-$300 million to develop.
While they require higher pre-investment costs due to a more complex regulatory pathways, higher manufacturing costs due to the complexity, the biosimilar business typically enjoys higher returns over time and brings significant upside to our margin portfolio. A good example of this is Omnitrope. As I mentioned earlier, this was our first ever launch eighteen years ago, and today, we are the leader in the market with a 38% market share, and this product is still growing today. Because the biosimilar is more affordable, then in some cases is offered earlier in the treatment life cycle, and so we tend to see growth of the market over a much longer lifespan.
Our midterm pipeline will offer 71 potential launches in generics, defined as a launch in the first major market, and seven biosimilars targeting around $130 billion of LOE originator loss at the point of market entry. In generics, we aim to cover in Europe about 80% of the global LOE to preserve the scale of our business and offset price erosion. Several launches will target larger generic opportunities like complex injectables and the GLP-1s. For the GLP-1s, it's the midterm opportunities that will be addressed through partners. Our plan is to be in the early semaglutide markets like Canada and Brazil, with partnered products to gather insights on the complexity, the regulatory frameworks, and the commercial landscape as we prepare for some of the bigger markets in the next decade.
In biosimilars, we have seven biosimilars to launch, and that cover about an LOE value of about $28 billion. In biosimilars, we're extremely excited about our recent and upcoming launches in immunology and oncology, bone disease, ophthalmology, and some particular therapy areas. Let's start with the recent launches. I'm really pleased that Hyrimoz in the U.S. has won the leading share position of adalimumab biosimilars, which includes both our private label arrangement with Cordavis and, importantly, our own branded Hyrimoz and unbranded adalimumab-a daz. This demonstrates our strong end-to-end capabilities across the organization. At the same time, we've been rolling out Tyruko across most of the major markets in Europe, where prescription has been extremely strong. And if you recall, we are the only biosimilar on the market, which makes this ultimately the closest I will ever get to an originator launch in my career.
We've also launched Pyzchiva in Europe about a month ago, and the initial feedback has been extremely positive. We will leverage again our strong market share, a portfolio of immunology products, as well as our excellent customer relations to drive growth. And we're also excited about many of our upcoming biosimilar launches. Denosumab, in particular, is interesting due to the multiple indications in both oncology and osteoporosis, which we believe has a significant market expansion opportunity. aflibercept is the opportunity space, and with the purchase of Cimerli, we now have a specialized sales force to call on retina surgeons. And you'll hear more throughout the day from some of the other speakers on our biosimilar launches and strategy. Moving to margins.
As you remember, we said at our Capital Markets Day last year, our goal was to increase margins from 18% in 2023 to between 24% and 26% by 2028. While I introduce this discussion, Remco will spend a great deal more time talking about how we plan to deliver this ambition. At a high level, we will do this through three primary drivers. Firstly, top-line growth of mid-single digits. We will be selling 30% more volume and will leverage our infrastructure. With the composition of our pipeline, we will benefit from our product mix, as well launching and growing our biosimilar business at a much faster rate than our generics.
Secondly, we have a series of operational improvements, which will drive the bulk of the expansion, including reducing our internal manufacturing footprint and our supplier network, optimizing our procurement spend, and focusing on vertical integration where it makes sense, and ultimately, utilizing innovation to drive operational excellence. And third, we've started the implementation of a transformation program, where savings of the second half of this year will then start ramping up throughout 2026. Just like we consider optionality in biosimilar development, we also continue optionality in manufacturing. With many of our current biosimilars are manufactured by our former parent, we have a long-term supply agreement of ten years, but which is based on a cost-plus arrangement.
We've recently increased capacity beyond the initial terms to keep up with the strong and growing demand, and at the same time, we're investing in building our own biosimilar manufacturing site in Lendava, Slovenia, which will give us capacity at even lower costs. While we have optionality with Just - Evotec, we're working with them on the development of multiple other biosimilars, which is going extremely well, and we have the potential to use their continuous manufacturing technology in the long term. Again, Claire will address some of this later on. In addition, we will use a number of CDMOs for surge capacity to address patient access, particularly where we see shortage of product in our market. As we think out further beyond the midterm, there's a significant opportunity for both generics and biosimilars with nearly $400 billion of LOE.
Starting at the top with the dark blue biosimilar LOE values, the expansion is more than double of what it has been in the midterm, with new technologies capturing roughly 25% of the biosimilar market in the next decade. Generics, however, will still also remain very attractive in the long term, with the size of the opportunity in standard generics remaining stable and a significant increase in the more complex end of generics. GLP-1s are the largest area of opportunity based on the size, and it's contributing two-thirds of the complex yellow LOE in the long term. As mature markets like the U.S. and Europe come into view, this supports our strategy to increase focus on this asset class in the future. Again, Rebecca and Claire will walk you through these new technology spaces later this afternoon and how they fit into our long-term pipeline.
So in summary, we are in a large and growing market. We are a leader in Europe, and we're extremely well-positioned in the U.S. and internationally. We have everything on hand to deliver our midterm guidance, both in terms of portfolio or our pipeline, and opportunities to simplify our business through our transformation plan. We have the internal resources to execute on our pipeline and have the scale to develop and attract strong partners to capture high-value, long-term opportunities. We have a strong balance sheet, which gives us the optionality for future technologies. All of this with the objective to deliver superior value creation for our shareholders and for society by pioneering access for patients. With that, I'd like to introduce Remco to the stage. Remco? Thank you so much. Very good.
Thank you, Richard, and good afternoon to all of you. Very pleased to see you here, and I hope I can spend some time as well talking with you in the, in the breaks, correct? It's my first Sandoz strategic review to discuss our midterm ambitions. During the almost two months, I'm now with the company as a CFO, I've got, of course, the chance to get more insights in many parts of the company, and it's only reinforced my confidence in our ability to deliver on our top-line growth and margin expansion. Let me start with our financial framework, which is a reminder of what we presented in the past. It's based on three main pillars, allowing us to invest in the future of our company and to deliver attractive returns to our shareholders.
Firstly, sales growth is supported by attractive market fundamentals, a number of key launches across markets, and the ability to leverage a strong and efficient commercial infrastructure. Secondly, margin expansion is benefiting from an increasing shift towards higher-value biosimilars, as well as numerous initiatives to simplify our business and operate as a truly generics company. Finally, the combination of margin expansion and efficient growth, efficient use of capital drives the third pillar, free cash flow growth. Cash is key to enable investments for the future, in our people, in our capacity, and in new technologies to ensure success for the coming decades, to pioneer access for patients and attractive returns for our shareholders. Today, I will focus primarily on the midterm. I will spend a good deal of time discussing our early achievements and the various initiatives that will enable us to reach our goals.
We are well-positioned to deliver on both the top and bottom line, including key biosimilar approval and launches, and a set of measures to drive efficiencies following the spin. Our organization is fully focused on execution. Achieving these targets offers us optionality to capture numerous long-term opportunities, ensuring sustainable success for our generics and biosimilar business. A month ago, on August eighth, we reported our first half-year result as a standalone company. Momentum continued to be strong, with sales growth of 7% in constant currencies. Biosimilar drove the growth, both from the base business and the recent launches. This led to a five percentage point increase of the biosimilar share of total sales from 22% to 27%. We expect this trend to continue in the second half of the year, aided by the launch of Pyzchiva in Europe in July.
As a result of the strong performance and outlook, we increased our full-year sales guidance from mid-single digits to mid- to high-single-digit growth in constant currency. Our core EBITDA margin declined versus the first half of 2023, as expected, though due to an inflationary impact on our cost of goods sold, which impacted us as of the second half of 2023. However, it improved significantly, 210 basis points, compared to the second half of last year, and within the first half year, as Q2 margins were higher than Q1. This was driven primarily by favorable biosimilar product mix, whereas the incremental inflationary pressure on cost of goods sold was minimal. During our earnings call, we confirmed our core EBITDA margin for the full year of around 20%.
As we look forward, the sequential improvement from the first half to the second half of 2024 will be driven by several things. Number one, continued favorable mix, as biosimilars are expected to become a larger proportion of sales. Number two, leverage our fixed cost base from strong top-line growth. And three, savings from our transformation program of approximately $50 million. Let me now turn to our midterm ambitions. We have set a clear target of increasing our core EBITDA margin from 18% in 2023 to mid-20% by 2028. The expansion will be a result of three main drivers: volume, mix, and price; operational improvements; and organizational efficiency. Volume, mix, and price is expected to contribute roughly 200 basis points. We expect strong volume growth across our regions and an increased shift towards higher-value products. This will partly offset by price erosion.
Price erosion has stabilized this year, but we continue to assume a low- to mid-single-digit price erosion in our plans for the upcoming years. Of course, we will monitor closely the evolution of price erosion. Operational improvements are expected to contribute the most with 350 basis points. This includes changing the way we procure and reorganizing our internal and external network to maximize efficiency in our supply chain. Organizational efficiency accounts for the remaining 150 basis points. This is all about transforming into a more streamlined and agile organization, aligned with being a true generics company. Let me now spend more time on each of these drivers, starting with volume, mix, and price. As I mentioned previously, we have been very pleased with the strong demand for both our base business and new launches, supported by eleven straight quarters of growth.
Biosimilar growth has been particularly strong with the recent launches of Hyrimoz in the United States and Tyruko in Europe, as well as the strong momentum in our base business, driven by Omnitrope. In the midterm, we expect to grow mid-single digits in constant currencies annually, with generics and biosimilars contributing equally to the top-line expansion in absolute terms. We anticipate that biosimilars, as a proportion of total sales, will climb from 27% in H1 to at least 30% by 2028, with multiple new launches coming later this year and over the next few years. This has a beneficial impact on our margins, with biosimilars historically showing, on average, a 20 percentage point higher gross margin compared to generics.
The momentum in the business will be supported by both our base business and the contribution of new launches, which target a large LOE of $130 billion in the midterm. Growing our top line allows us to leverage our existing commercial infrastructure as well as our fixed cost. As a leader in generics and biosimilars, we provide 800 million patient treatments every year in more than 100 markets. We make 1,500 products available to patients worldwide. Growing these products across geographies allows us to maximize utilization of our sites, positively impacting our margin through leveraging our fixed cost. We believe that we have a leading commercial presence for oncology, immunology, cardiovascular, and infectious disease. Many new launches are targeting these therapy areas and require limited additional investments, which offers further margin improvement.
The second and largest driver of margin expansion relates to operational improvements. Roughly two-thirds of the operational improvement is related to procurement. Coming out of a large pharmaceutical company, we see many opportunities to streamline the way we procure across the organization. We're implementing a segmentation of close to 50,000 suppliers to create a fit-for-purpose supplier ecosystem. At the top, we have roughly 60 strategic partners with which we continue to actively engage. We want to create value through collaborations around shared goals. As an example, we're working closely with Amcor to develop sustainable and cost-effective packaging solutions. We're unlocking gross margin improvements through a set of transformative value platforms focused on direct materials, contract manufacturing, and indirect spend. Key examples of initiatives include the alternative sourcing program, aiming to halve the time for alternative source approvals and finished dosage form technology transfers.
We initiated the so-called Triple S, which is the Sandoz Smart Spending Initiative, focused on optimizing indirect spend and cost while fostering cultural change and smart spending practices. We're also planning to improve the efficiency and effectiveness of our purchasing processes through standardization and technology. We have significant opportunities to reduce the number of contracts and standardize them. Adding digitalization will drive insights and analytics, allowing more efficient negotiation with our suppliers. The remaining operational improvement opportunities are split across network design, focused vertical integration, and operational excellence. Several initiatives are currently underway to deliver on our targets. In network design, we're ahead on our planned reduction of internal manufacturing sites, with a target of fifteen sites already expected to be reached by the end of this year. On the external network, we're also progressing on consolidating and prioritizing our suppliers.
For API suppliers, we're willing to maintain a broad set of roughly 300 qualified partners, which we can leverage to competitive tenders. As a leading generics company, there's a strong willingness of these partners to collaborate with us. For finished dosage form, we're well on track to halving the current 400 suppliers by 2028. We're already in the process of exiting 100 suppliers, and the remaining part has been identified. We've also made good progress on vertical integration. We have recently inaugurated the new antibiotic production facility in Kundl, Austria, leading to a doubling of capacity compared to 2021 output levels. On biosimilars, we're progressing according to plan on the construction of a manufacturing plant in Lendava, in Slovenia. We expect the plant to become operational in 2026.
It will then take eighteen months to about two years to tech transfer products, so we expect first commercial manufacturing in 2028. In addition to network design and vertical integration, we're executing on multiple operational excellence initiatives, including investment in automation at selected sites. Moving now to the last driver of margin expansion, organizational efficiency. We have been working hard in transforming our organization to become a more fit for purpose, more agile, simple, and more efficient. Coming out of a large pharmaceutical company with a much more complex and layered infrastructure, we have plans to reduce layers across the organization and simplify processes. We spent the first half of the year identifying the scope of the opportunity and communicating with our workers' councils across the various countries we operate.
While we're still working with certain countries, others have been completed, and we have now moved into the implementation phase. We're already noticing benefits in our way of working. This will be a multi-year program through 2026. We expect to incur costs of around $350 million, primarily related to personnel costs. In the first half of the year, we took a provision for $140 million. Depending on the timing of implementation of some of the remaining countries, we will take another similar provision in the second half of this year, with most of the remaining expenses in 2025. We expect to see the first major savings benefit of $50 million, as already said before, in our second half of 2024.
This will increase further in 2025 until we reach the full run rate savings in the range of $200 million by 2026. This program, which we're classifying as organizational efficiency, underpins our plans for the 150 basis point margin improvement in the midterm. The transformation program, together with our one-off separation required to transition to a fully independent company, will incur costs in 2024 and 2025 that will be adjusted from our core P&L. I just discussed the reasons for the transformation program. The separation activities are primarily related to setting up a standalone IT infrastructure and building up manufacturing and development capabilities post-spin. We expect 2024 to be the peak year, with around $600 million of cost, decreasing to around $400 million in 2025, with limited cost thereafter.
This is about $200 million higher than our original estimate pre-spin, due to a more complex and intertwined infrastructure of our systems and business processes with our former parent. Our strong balance sheet supports the required investments in separation and transformation, as well as for future growth. For our debt financing, we successfully completed bond issuance in CHF and EUR in the month following the spin-off. We are benefiting from a well-balanced maturity profile, with an average maturity of gross financial debt of approximately five years. Our equity has remained stable around $8 billion and compares to a net debt of $3.4 billion by the end of June 2024. We're targeting a net debt to core EBITDA ratio in the range of two times in the midterm.
We have solid investment-grade ratings, placing our company in a strong financial position to support our ambitions. Expanding our margin in the midterm will have a direct impact on the free cash flow generation, especially once the years of large investment in our separation and transformation are behind us. From 2026 onwards, the cash flow generation will support additional investments in key capabilities, including GLP-1s, I know many of you are interested in that, and upgrade of IT systems. We are currently evaluating the additional CapEx requirements for these specific items. What I can share you is the following: GLP-1 related CapEx will be mainly fill-finish capacity. Some of this is in our existing plans for fill-finish capacity for our complex injectables, which leverage existing sites.
The additional CapEx requirements are expected to be in the hundreds of millions CHF, with the exact amount highly dependent on the final split between in-house manufacturing, on the other hand, collaboration with partners. As Richard mentioned, launches in the early markets will happen through partners, and hence, most of the additional CapEx is expected to be beyond 2028. As part of the spin-off from our former parent, we signed a TSA to transfer all systems to our own standalone environment. We're running about 1,500 shared software platforms and are actively working to transfer some of them. Additionally, we try to limit dependencies, which will help us once we start upgrading systems. Some of the key systems we are inheriting, including SAP, will need to be subsequently upgraded and redesigned to be fit for purpose.
Excluding the additional CapEx requirements I just discussed, the manufacturing CapEx remained unchanged to what we communicated last year. We expect to invest $2 billion between 2024 and 2028. Half the CapEx, or closer to $1 billion, is related to the replacement and expansion CapEx, in line with historical average of roughly 2% per annum. The remaining $1 billion is related to biosimilar investments, with the Lendava, Slovenia, manufacturing site accounting for most of the spend and additional capacity required for the increased volume. Our capital allocation priorities remain unchanged in the midterm and are fully aligned with our strategy. First and foremost, we will invest in our organic business. This includes the separation, transformation, and manufacturing investments I just discussed. These investments are key to ensure sustainability for our business. Secondly, we plan to pay a dividend according to our previously communicated guidance.
We paid our first dividend in May, representing 24% of our full year 2023 core net income. We'll increase the ratio to 30%-40% towards the later part of the midterm plan as we move into more cash generative years. Lastly, we're targeting both on M&A and BD&L as a way of selectively adding products to our portfolio. We expect that $200 million-$300 million of investment will add approximately one percentage points of inorganic growth to our top line on an annual basis. This is best highlighted by the acquisition of Mycamine in 2003 and Cimerli in 2024. In summary, we're well-positioned to deliver our midterm ambitions. Our hard-earned work since the spin has led to strong results to date, will position us well to reach our midterm guidance.
We have strong momentum in our business, which will be aided by several launches across key markets in the coming quarters. Additionally, we have put several programs in place that will drive our margin expansion over the midterm. Our goal of a 24%-26% core EBITDA margin by 2028 is a journey, not a destination. And with that, thank you very much for listening to me today, and with this, I will hand it over to Richard to open up for the first Q&A session, for the sessions you heard so far. Thank you very much.
Before we start, is this on? No. Yes? Okay. Before we start the Q&A, I just ask that you wait until somebody brings you a mic. Since we're webcasting, we want to make sure we're capturing everybody's questions. With that, I will let you take over.
Thank you so much, Keren.
Question here.
... Thank you. Can you hear me? Lovely. James Gordon from J.P. Morgan. I'll do two questions, please. One was, you talked about launching generic semaglutide ex-US from 2026 , and I think you said that you would use externally sourced API and a mixture of fill finish externally and internally. But in terms of the devices, I've seen some nice devices out there, but do you have lots of device capacity yourself, or would you source that externally? What's the plan there? Might you need to make significant investment in being able to produce a lot more devices to serve those ex-US markets? That's the first question, please.
In the short term, no. I mean, I think we have most of it, not necessarily all device-oriented, depending on the product. I mean, our first priority is to get it to market, and I think that will be ultimately with a simpler device. Over time, then we would look at potentially bringing auto-injectors and... Because I think the market will stratify. I think it will, you know, you'll see a differentiation move, I think. And also, bear in mind, most of the capacity we're going to invest in, we needed the injectable capacity anyway. Ultimately, we're an injectable business, particularly on the biosimilar space. So where we're investing is really multi-use capacity. I know everyone's sort of very focused around billions of dollars.
I see this more in the hundreds of millions of dollars, and that's why ultimately it's going to be a combination of in-house and a number of partners to get there. And quite honestly, as Rebecca will talk about in a little while, I've got no idea how these markets are going to evolve. I mean, whatever I tell you is going to be wrong. You know, so clearly, we're focused on bringing the product to Canada, bringing the product to markets like Brazil, and using that as a learning experience as we then think about the next wave, which is really going to be the North America side of the 2030s.
Thanks. So just to make sure I followed that correctly, is it that somewhere like Brazil, you might initially launch the product without it being in a-
Correct
... the same device as well?
What's more important is to be at market formation. I want to be at market formation, and I'd rather be in a simpler device to be there and then potentially introduce more complex devices over a period of time. Maybe that gives you, you know, an opportunity to segment the market to different patient needs and, say, patient classes. But the first priority is get there in market formation.
Thank you. And then, the second question was, Stelara biosimilars for the U.S. So how big an opportunity should we think that as being, and is what's ended up happening with Humira and CVS a good guide for how something like that might go? Or is... Should we think of Humira more as a one-off that's gone surprisingly well and don't extrapolate that?
Respectfully, can I let Keren talk about that, and then we. It's a great question, but I think let Keren talk about it, and then we can address that way because I know it's a common question that we get.
Sure, well, thank you.
Thank you.
Hi, thanks. Emily Field from Barclays. Two questions. Firstly, you mentioned that the Slovenia biosimilar manufacturing facility will be at a lower cost. You know, I know that the Novartis arrangement is, you mentioned cost plus, but if you could just provide any sort of context or order of magnitude behind that lower cost. And then the biosimilar margin, you mentioned 20% higher gross margin, but I was just curious how that translate also into EBIT margin, given, you know, perhaps some level of promotional cost. I know the development cost is higher, but just, would figure SG&A is probably a little bit higher on those. Thank you.
I mean, I'll perhaps address the first part. I think, Remco, if you want to take the second part.
Mm-hmm. Yep.
And look, we don't disclose our cost of goods, but clearly, at the moment, I mean, it's going to be certainly we're not paying the transfer cost or the markup that Novartis will provide. Clearly, we will design Slovenia in mind in terms of capacity. We intend to put a significant amount of volume through, which gives us leverage. And also, as Claire will talk about a little bit later on, it also then, over the time, potentially we will choose to put in pod technology from Just - Evotec, which also then could be a significant step change in terms of cost of goods. So I think there's a number of steps. Our first priority is get the site built. It's not an easy thing, tech transferring, so getting a portfolio of assets tech transferred into that facility.
And then ultimately, I want to build a broad optionality, so not every egg is in one basket. So clearly, we will potentially continue to use Novartis for surge capacity as we use a number of CDMOs. But I think what's important is getting the foundation built in Slovenia, then that gives us the leverage to make choices in the future. Remco?
Yeah. Emily, nice to see a face behind the name. Nice to meet you. With the biosimilars, we say by purpose, on average, 20%, 'cause within biosimilars, there are different gross margin. If it's a completely only developed product, you can imagine the margin is much higher than when it's a licensed product. So this is on average number. I think that's important to keep in mind. We don't disclose exactly what those margin are. You can understand why. Below the gross margin, it's indeed correct, so the R&D portfolio is, for significant part, also on the biosimilars, but equally also on the generics portfolio. For us, what you've seen also in the margin improvement, it is to steering those mix over time, both within generics and making biosimilars a bigger part of the overall portfolio.
So if you then look at the cost below and you look at the sales and marketing, I think for us, the game is more we have a very strong commercial infrastructure, and build on that, and don't grow it too much, and change the portfolio with that existing structure, and in that sense, leveraging. That's more than you can really allocate it to one or another. It's one commercial force, which will, over time, gradually sell more biosimilar, let's say, a better mix within generics. That's, I think, the way to look at it. And of course, our corporate headquarters, we just moved to a nice place in Basel, but it's one floor, and we try to keep it simple and at a cost level which fits with the generics-
No din, no dinosaurs. Other than me, maybe.
Then I'm with you, too.
Hi. Holger Blum, Pareto Securities. A question on the financial guidance for the better margin outlook for H2. Clearly, it makes a lot of sense that you have more volumes, operational leverage, cost savings, mixed benefits.
... All these arguments would hold true also for 2025. So maybe you can help us bridge from the second half 2024 to the first half 2025, and the second half-
Uh.
2025. If you make similar 400 basis points improvements, half year over half year, you'd be quite high.
Yeah, we are very quickly at 100%, correct? And mathematically, that doesn't work anymore.
Now, of course, there is quite a difference when you compare it over the period, correct? But you have also to see that in the context of the improvement areas. That's why I tried to, at the beginning of August, to elaborate a little bit on the different factors, correct? One, of course, is the mix, correct. If you do your math, you see that the top line in the second half is a bit higher than in the first half. So you have, of course, leverage on the fixed cost base, and our transformation program is kicking in. You cannot apply that just in a straight way again, to the next year.
As well for next year, we have to think, what will price erosion be? For us, it's too early. It's relatively low this year. The inflation we see in our product cost, it seems relatively low at this point in time, but we still want also to make the improvements on the cost price, so make the procurement savings in the system. And of course, then there is as well, how much money we allocate to our R&D expenses, R&D expenses. Because there also, we have to take a midterm view, particularly on our R&D investments, and we've also not decided on what level we end up. So I would caution by extrapolate that going forward. But one thing is clear, correct, we want to reach those midterm numbers of the 2024 to 2026 by 2028.
So you can expect, correct, that we are targeting every year an improvement. But that amount of improvement every year, it will be lovely, but it's at this point in time an unlikely one. Yeah. Sorry to disappoint you.
Thank you. Emmanuel Papadakis at DB. Maybe a question for Remco on free cash flow. You've reiterated the 2028 guidance for a couple of billion, 70% EBITDA conversion rate. Obviously, recent performance has been a little more challenging, so perhaps you could just talk about the bridge to get there. From the schematic you presented, it looks like it's now a hockey stick. So what does H2 this year, 2025, look like from a free cash flow perspective?
Uh.
Should we really expect that to inflect in the later period of that guidance range? And then perhaps a question on margins, on biosimilar products. You've talked about them being significantly ahead of... I think you commented, Richard, on the Q2 call, to the tune of 30% ahead of the generics business. Could you talk a little about, within biosimilars, the, the contribution margins on private label versus branded? Obviously, you've benefited tremendously from the partnership with Cordavis on Hyrimoz. What are the... I think you've commented in the past, actually, margins are pretty similar. Could you talk a bit more in detail about that and how you expect that to evolve going forward? And indeed, what's the incentive for PBMs distributors to partner with you if there is no economic benefit? Thank you.
I start with the free cash flow one.
Please do.
I think first and foremost, it is when you look at this year and when you look at next year, to look at the free cash flow with or without the non-core adjustments, correct? And the non-core cost this year of CHF 600 million, and next year is still CHF 400 million. Of course, it's a lot of this. To help with a little bit more the insight, I was also a bit struggling coming in, how healthy is the free cash flow? For that reason, we introduced that management of free cash flow to give an approximation of the free cash flow, excluding those costs. So that is, if from here, you take the view, and you park this, correct? The EBITDA will move up in the coming years.
You have seen that we have done a relatively good job in the first half year on the working capital, plus the other elements, the gross to net kind of accruals, which we have in the systems. That is a relatively low increase. We expect that to continue in the coming years. Of course, there are interest expenses. You can also do the math on that, and there's the tax cash, which goes out. The remaining part is really on the CapEx. With the CHF 2 billion, we have given you some idea on the CapEx. We said as well that we're evaluating what we do in-house, not in-house, and whether we do something more in the later years of the midterm guidance and increase that amount. IT could be an element, correct, which we are elaborating.
But still, if you do that over the coming years, you will see that there is ample opportunity on the free cash flow if you do the math. But these first two years, 2024, 2025, is significantly impacted by the non-core cost. With regard to the second question, correct, on the margins of biosimilars, and unless you have another view on that, Richard, I think it wouldn't be wise for us to really disclose. That's it. I understand it from your perspective, correct, to understand what deals we exactly do and what margins are behind that. But from a commercial perspective, it's not really, you know, really wise for the company, so sorry for that.
To your latter point, you're right. I mean, really, on... I'll let Keren again no doubt talk about Adaz in the U.S., but really, because of a whole bunch of factors, net-net, it's about the same. So whether we sell our own label product or we sell Cordavis product to the business, it's about the same.
Good afternoon, Florence Cespedes from Bernstein. A quick question on the... You said that you have a leading presence in oncology, immunology, cardiovascular, infectious diseases. Could you maybe elaborate a bit on what is your competitive advantage on each of the different sub-segments, notably infectious disease? I suspect there is not much competitors here. Some color on the different sub-segments-
Yeah, I mean-
Would be great.
I think, I mean, it's growing in terms of the U.S., but particularly from a European lens, I think one of the moats that we have, I don't... You know, we don't talk about it enough, quite honestly, is every market in Europe looks different. You know, so clearly, healthcare system in Germany is gonna look very different to the healthcare reimbursement system in the Netherlands.
So we're very in tune with the market. That's actually very hard to build bottom up, and a lot of the questions I get is, you know, I mean, the Indian generic companies have been coming for the last 30 years. They're still not here. So it's tough. And because the bulk of the biologics that we've launched have either been in immunology space or the oncology space, and we already had a strong presence. So in Europe, I think we're the biggest immunology company, we're the biggest oncology company. So the key point there is when we launch, so just as we've launched ustekinumab now in Europe, we don't need any more sales force. We have the relationship with the payers, we know how the market works, and we're in tune with that individual market, and so we're able to leverage it.
Now, clearly, yeah, an in-licensed product is not as margin accretive as a fully developed product, but equally, it didn't cost us CHF 200 million to develop. So it's nice to have the combination, too. So I think that's really the key point. In the U.S., now, when we launch ustekinumab, we already have an adalimumab capability. We already have a strong immunology presence, which clearly we can leverage. So we don't need any more capacity, we don't need any more sales force. We have the relationship with either the PBMs or, and/or the customers or the insurers. So, that's really the point I'm trying to make. Thank you.
Thanks. It's Graham Parry from Bank of America. Just a question on midterm guidance. What's your threshold for changing that or raising it? You've obviously been outperforming adalimumab. I think it's outperformed most people's expectations. U.S. pricing looks better at the moment, but it could be short term. What would see a shift in midterm guidance? Second question is growth beyond 2028 . Could you actually envisage that you could see top line accelerate through that time frame, just given GLP-1, lots of other biosimilar opportunities coming through there? And then lastly, on API for GLP-1, you've indicated that you'd look to do that externally. Is there enough global capacity for API for GLP-1 to satisfy the market over the mid to long term, do you think?
have to do the GLPs, and I'll let you take the other part.
Okay.
Thank you. I mean, at the moment, our view is yes. But that's ultimately why I said, you know, in a sense, Canada and Brazil are sort of almost an experiment, because I've in my career, I've never launched a drug quite like this, how I forecast it, how I think about it. And so, you know, certainly at the moment, we have a number of partners. We're confident we can supply the demands that we forecasted. And clearly, I could be wildly wrong with my forecasts, but we will see. I mean, that'll be a nice problem to have, I guess.
Your question, correct, of raising midterm guidance, thank you very much for putting that challenge in, in front of me, in front of us already. I think time is the question, correct? We just spun last October, correct? We're hardly a year in. Two years develop. Of course, we will try our best to exceed those targets, and if then the time is there, we will certainly come back. Of course, after 2028 , correct, we want to further grow, correct? We want to further develop the margin, so normally you would expect it to go further up. If you also look in the field of competitors, correct, and then the mix further developing, you would expect that. But again, it's very early days, correct, to comment on that time frame. Yeah.
We just have a couple more minutes, so maybe one more, and then we're gonna, we're gonna do Q&A at the end. We have plenty.
Well, it's kind of two to four minutes.
That's fine.
So, yeah, two questions.
I'll just keep the question to one then. It's James Vane-Tempest from Jefferies. Thank you. You've done a number of strategic collaborations this year with, with PBM, so I guess one of those contracts sort of due to be renegotiated, given the high volumes you're seeing as a result, potentially if more patients start using biosimilars. Thank you.
Can I let Keren answer that one? 'Cause... So good question, but, I won't steal Keren's thunder.
Brilliant. Then I'll jump in. Hi, it's Harry Sephton from UBS. So just one on capacity. So you mentioned that you've got increasing capacity with Novartis beyond the initial terms of your agreement. What I wanted to understand was how much more additional capacity do you have from Novartis? You're not really going to ramp up your own biosimilar capacity for a number of years. So if you continue to see such successes as you have with Humira in the U.S., what ability do you, are you-
But clearly, I mean, it's a win-win. In a sense, Novartis love their recoveries and like driving the volume, so we're delighted, and clearly, we'd be able to take additional capacity over the original MSA contract terms. It's beneficial, clearly, to our business and to our patients. And then it also then supports our midterm strategy to move into Slovenia. And then ultimately, I wanna make sure we have optionality. Just because we have Slovenia, doesn't mean we necessarily walk away from Novartis. Clearly, I wanna leverage Slovenia as hard and as fast as possible, but having additional surge capacity. One of the problems with this industry, with really the exception of natalizumab Tysabri, we don't never supply 100% of any market.
So, you know, if one of our competitors has a volcano blow up near their manufacturing site, for instance, how do I respond to a 25% market shortfall overnight? No, no supply chain can manage that, and particularly in biosimilars, where we're forecasting at least a year, eighteen months out in terms of volume demand. So I think having some flexibility, even if it necessarily comes at a higher cost, is important to be able to respond to those sorts of events. So I want a sort of a broader base of supply, clearly centered around Slovenia, and then leveraging different partners over a period of time, particularly on drugs like adaz, which clearly we see continuing to grow really for many, many years from now. Okay, I think we're pretty much at time.
We are at time. So we're gonna take a fifteen-minute break. We'll reconvene here at 3:15 P.M., and we'll start our second round of presentations.
Welcome.
Thank you.
... Thank you, everybody, for coming back in. We're going to start this afternoon with Keren Haruvi, who's our President of North America, and she is going to answer all of your questions related to that region.
Thank you, Keren, and thank you, Richard, for allowing me to answer all the questions later. Welcome back from the break. Pleasure to be here with you today. You know, it's been almost a year since I last updated you, and I'm very excited to share with you all the progress and success we had in North America. So during the presentation, I'll cover where we are today, our key initiatives, focusing, of course, on the exciting launches to deliver the midterm, and we'll take a look on how we'll remain a successful player in generics and biosimilar in the long term. Let's start with the market, the overall North America market. The market is $79 billion, almost $80 billion market, with 9% CAGR expected in the next 10 years, mainly driven by growth of biosimilars.
Our business, as of 2023, is a $2.1 billion business, again, mainly growing for biosimilars. We are strongly positioned in the U.S. and Canada. We rank number 4 in the U.S. and second in Canada. We have 8 biosimilars currently in the market, and as you can see, we have leadership position in many of those products in the market. We have exciting. Probably the most exciting piece of my presentation will be talking about our upcoming launches. We have four launches coming. I do want to note that Wyost and Jubbonti, our biosimilar denosumab, we already launched in Canada, recently launched, but it's still pipeline for the U.S. And last but not least, we will cover the exciting pipeline that we have in generics, which covers North America, 130 products. So talking about our position in the market, let's start with the U.S.
Our share is 4%, almost 4%, and we rank number 4 in the market. This is consistent with our strategy of stabilization of the market. If you look at Canada, we're number 2, ranked number 2, with 11% share, very close to the number 1 competitor in the market. It's a local competitor, and definitely we have the aim to become number 1. I'll focus today mainly on the U.S., so let's shift the focus on the U.S., and I love to tell our story in three chapters. Chapter one is the stabilization of the business, that I'm very proud that we achieved. Chapter two is where we are today, and I'm excited to say that we are growing, and I'll share in a second how we are doing it.
Chapter three will be how we're going to sustain this growth in the future. Let's start on how we are doing today, and I'll start with the biosimilar market. We're number four in the market with 11% share, and we are outpacing significantly the growth in the market. We have in the market a portfolio for some time. You know, I'll start with our Omnitrope that we launched in two thousand and seven, our growth hormone, and we still have a leadership position in the market. We also have Zarxio. We were the first company to introduce biosimilars into the United States in two thousand and fifteen with our oncology product, Zarxio, and we're still the number one player in the market. As you can see, long commitment to patient in this space. Earlier this year, we acquired Cimerli. It's a biosimilar ranibizumab, biosimilar Lucentis.
We did this acquisition really to pave the way for our future launches in the ophthalmology space, in the retina space. Last but not least, as Richard mentioned, our Hyrimoz, and I saw that you have a lot of questions, so I'm sure we'll cover more than that. It is a good opportunity to go a bit more detailed on Hyrimoz. We launched Hyrimoz in the U.S. in July 2023. We didn't see much pickup. I must say, at the end of 2023, overall biosimilar share in the market was less than 2%. It is very disappointing for the largest-ever LOE.
We decided to collaborate with one of the PBM, with CVS, with their entity, Cordavis, with the first and, I would say, one-of-a-kind agreement to bring private, private label, you know, biosimilars into the United States, and that create a huge change in the access. So in April 2024, Cordavis displaced Humira from their formulary, and that created significant access to patients in the market. As of today, as you can see, this is all IQVIA data. 90% of the market is held by biosimilar. Still, 81% of the market is held by the innovator. Out of this 19%, we hold 80% of the market. It's a combination of the deal with Cordavis and our own branded Hyrimoz and unbranded adalimumab-a daz. As Richard mentioned, we are very proud we are number one, not just in the private label.
We are number one biosimilar outside of the private label. We'll continue, you know, to execute and fight this market, keep evolving and changing. Again, I will cover a lot of your question later, but we'll continue to execute and perform in this market. Now, we're going to change the shift to generics, which a very different market from us, and it's very different also from our ambition and position in the market. I would say also that it's very different than our ambition in the other regions at Sandoz. So you heard Richard said we're not aiming to be number one. As you can see, we are number nine in the market with 3% share. Now, let me explain a bit the why. So first of all, the 3% that we see here, it, we are selectively kind of choosing the portfolio for the U.S.
We are actively playing currently only in 15% of the market. So if you look at the market that we actually, the product that we actually have in the market, we have 19% share, versus the 3% that you see here, because many of the molecules in the market, we're just not playing. Now, some of it, as you can imagine, is the historical gap in pipeline that we have. We talked about it a lot last year, the fact that we tried to divest most of our oral solid and derm portfolio in 2018. This divestment didn't pan out, and actually, we integrated the business back in 2020. It takes time to build pipeline. So what you see here is some of it, it's just historical pipeline gap.
Also, what you see here, and I'm sure you all know, the generic industry in the U.S. is very challenging. I like to describe it as a triangle, you know, with three sides: price, quality, and supply. Prices are too low. Prices for generics in the U.S. are too low. As I keep saying, as an industry, we did too good of a job. Quality is non-negotiable, and then unfortunately, where you see the impact is in the supply. That's why you see in the United States, the highest ever drug shortages. Now, we are going to continue to leverage our global portfolio, but we are gonna introduce molecule into the market only when we believe that we can reliably supply the market with a relentless focus on quality.
So as Richard said, we're not aiming to be number one, but we are aiming to be a sustainable player in this space, and later I'll cover the pipeline that we have and why we are confident that we can remain a sustainable player in this space. So that's the today. Now we are shifting to the midterm. How are we gonna continue to grow in the midterm? So our strategy has three strategic focus. One, become leaders in biosimilar. Second, as I mentioned, sustain the growth in generic, and third, to be the best commercial engine in the industry. So before I talk about how we're gonna become a leader in biosimilar, I wanted to talk a bit about the market. As you know, in the U.S., biosimilars can be sold in two channel, the pharmacy benefit and the medical benefit.
They are very different dynamics, and I thought to kind of focus on the main difference. If you start with the pharmacy benefits, the prescriptions are filled at the pharmacy and administered usually at home by the patient. The adoption is driven by three PBM that control 90% of the formulary decision. So if you think about it, if you are not on formulary with the PBM, the patients will not get access to the product. As we talked, we saw the introduction of private label into this space. Again, our agreement were the first ever, but we do anticipate that this space will continue to evolve. We have two product in the market, in the pharmacy benefit, Omnitrope, our growth hormone, and of course, Hyrimoz. Looking at the medical benefit, you know, it's physician administering the product for the patient.
It's being done in the hospital or, you know, clinic setup. That's where it's much more fragmented kind of customer base. The customer base is either the healthcare provider or GPOs, and adoption is really driven by their ability to create cost saving. As you know, in the U.S., the medical benefit is playing by the buy and bill model. So basically, the hospital or the clinic, they buy the product, they administer to the patients, and then they get reimbursed. So very different dynamics. We have three product in the market in this space, a lot of experience in both oncology and then Cimerli, you know, our recent acquisition.
Now, this is the most exciting slide, and you need to bear with me because I'm gonna give you a lot of details on each one of our launches, but this is really how we become a leaders in biosimilars. We already have a great platform, as you heard from Richard, in immunology, oncology, now ophthalmology, and this will serve as our launching pad into the future. Now, a lot of progress was made since I last presented to you, and I'll go to each one of these launches in a bit more details. Let me start with Pyzchiva. This is biosimilar Tocilizumab. This product was not in our portfolio last time that I presented, given this is, Richard mentioned, a deal we had with Samsung. We are very excited from this opportunity.
We will be able to launch in Q1 2025, according to the settlement that Samsung reached with J&J, and will be in the first wave of product in the U.S. This will leverage 100% our infrastructure and capabilities in the immunology space. So really taking all the experience that we have now with Hyrimoz, and we will leverage it here. If we look at the medical benefit space, we have three very exciting, I would say, launches coming. The first is Tyruko, is biosimilar natalizumab. This is a collaboration with Polpharma. We gonna be the first biosimilar into the MS space, the multiple sclerosis space, and we are uniquely positioned here because this is a very complex product from a safety perspective.
And we believe that with our experience in biosimilar and our experience with patient support, we're well-equipped to support those patients through their, through their disease journey. Now, as you can see, we have an update here about the launch date. We guided in the past second half of 2024. We are still discussing with the FDA. We recently got feedback from the FDA on the JC virus assay. So just to remind you, the BLA and the REMS are already approved, but we do need approval of the JC virus assay in order to launch in the U.S. So we will keep you posted how we progress. But again, this is really recent update, and we are working and engaging with Spar pharma and the FDA. Next one is Wyost and Jubbonti. It's actually two products.
It's a biosimilar denosumab, in the space of oncology, Wyost in oncology, and Jubbonti in osteoporosis. We are the first to get FDA approval, so we're very excited from the opportunity to be first in a very competitive market. We're gonna launch in Q2 2025. We settled with Amgen, and again, we see it as a huge win. Last time that we presented to you, we didn't have a certainty of a launch date. By having this settlement, we are well kind of ahead and prepared with our commercial preparation for launch. Again, also here, we're gonna leverage our experience and capabilities. So with Wyost, this is going into our oncology platform, and it's gonna be exactly the sales team that we currently have for our oncology portfolio. And with Jubbonti, with the osteoporosis, we have significant overlap with the prescribing physicians for the immunology portfolio.
So we are really excited and getting ready to launch this. And last but not least, Enzeevu, this is biosimilar aflibercept, and this is, as I mentioned, we have now the capabilities in this space through our acquisition of Cimerli. So we have now a sales team, and we have the commercial relationship and capabilities in the space that will pave the way for this launch. We don't have a date yet. The IP landscape is very complex. I'm sure you are following. So as we know more, we'll keep you updated, but we are working to give you the certainty, and once we know, we'll update more. So I covered a lot. I'm sure I created more questions than answer, but, we'll get there in the Q&A. Okay, looking at our generic generic pipeline, again, very exciting and broad pipeline.
As we said, we are closing historical gap. So as you see, 2024, still our number of launches is very limited, but as we move on, 70 products, it's pretty impressive. We are planned to have those launches both at LOE and kind of first-to-market opportunities. So just if you think what Richard presented in the beginning was only LOE opportunities, here we show both LOE and first-to-market opportunity. Other than that, it's pretty balanced between standard generics and complex generic. And as I say, we'll continue to leverage global portfolio. That's what we are doing here. We're leveraging the portfolio. As you know, if you want to enter the U.S., you need to develop the product few years before, but we are gonna develop only the products that we can leverage in Europe and in international.
Looking at the long term, we talked about the market growing 9%. 25% out of this will come from biosimilar. This is super exciting time for biosimilar in the United States. I keep saying to my team, "We are writing history." And to remind you, our purpose is to drive access. That's what drive access into United States. Currently, 2% of the patients in the U.S. are getting access to biologic drug, but the cost for the system is 50% of the drug costs in the U.S. So there is a huge opportunity to allow more patients to get access to biosimilars, and we are committed to continue to drive and make sure that patients get the product they need at the right time and at the right cost. Now, we're not going to do it alone.
We have a lot of stakeholders that we are working with. Personally, I'm the chair of AAM. This is our industry association for generics and biosimilar. This allows us a strong voice to improve and change the healthcare system. We are working closely with the FDA to make sure we continue to streamline the regulatory process and, of course, with other agencies, other government agency, to continue to drive social impact. I think it's clear to many of us that advocating for sustainable healthcare system in the U.S. is key. 90% of the generics product in the U.S. are generic. Sorry, 90% of the medicine in the United States that are filled with generic. So it's super critical. We'll continue to push to a more sustainable healthcare system.
So I hope by now I made it clear that we have everything we need to continue and lead in North America, but there are five reasons to believe, and they are all here on this slide. First of all, we have a very attractive market, and as I said, this is the time. We are writing history in biosimilars in the United States. We have a great strategy, which is panning out by being a leader in biosimilar and keep being a sustainable player in generics. If you think about it, our plan is that our launches will offset, you know, the price erosion in the market, so we'll have a sustainable base on generics, and the growth will come from biosimilar.
We have strong pipeline in biosimilar, strong pipelines in generics, and most important, we have the scale, the people, and the culture to continue and drive this and make sure that we do what we know to do the best, which is serve patient. So thank you. I'm looking forward to the Q&A, and with this, I will hand over to Rebecca.
So good afternoon, everyone, and it's a pleasure to be here with you today. I see some familiar faces I already saw last time when we presented in London, in New York, or even in Zurich, and today is my first presentation actually in my new role as Chief Commercial Officer, which I just started this week, meaning yesterday. This doesn't mean that I'm new to the company. I've spent my last 17 years in Sandoz, and the last five years leading the European business, which accounts for 50% of the global sales. So as the title outlines of this session is, there is significant opportunities in the market. And I'm really looking forward to continue to strengthen our industry-leading pipeline, which of course is absolutely key for the long-term success of the company.
Today, my objective of the presentation is to provide you clarity and visibility on three main aspects. The first one is the question: how do we actually select the pipeline? What is the strategic framework? The second one is how our pipeline is aligned with the evolution of the LOE landscape, the loss of exclusivities. And third, to provide you with early proof points on our ability to deliver on the pipeline in the mid and long term. So since we met the last time at Capital Markets Day, we really have advanced on so many of our commitments and remain focused on delivering on our growth and margin ambition. In biosimilars, we have completed two submissions, we have received eight approvals, and we have launched three products while expanding the biosimilar portfolio in the U.S. with the acquisition of Cimerli.
But also in generics, we have launched over 130 products, building on our strong in-market position and leveraging our scale across the region to drive sustainable growth. Today, I want to focus on the opportunities in the mid- and long-term of our pipeline to create sustainable enterprise value. On this slide, you can see the LOE landscape, and what you can also see, that we see significant opportunities in both the generics and the biosimilars. The size of the addressable market for us will significantly increase over the next 5 to 10 years. The largest LOE growth is coming from biosimilars, and as you can imagine, this creates an opportunity for us to leverage our existing capabilities and of course, the commercial infrastructure you have already heard a couple of times today.
Generics remain and provide us a robust base business, which is really delivering scale and customer access across the markets. Last but not least, the largest new category, GLP-1s, will offer significant value as this market is expected to exceed $150 billion by 2035. Let me share now the selection framework. Developing assets like biosimilars and complex injectables is costly. As a company, we need to maximize the opportunities with the capital we have actually on hand, which means we have a very disciplined approach in pipeline selection, which is based on four key principles. First, we want to develop programs with launch at LOE, which provide us scale and span across major markets, because we all know this is driving the biggest and largest commercial value. Secondly, the commercial lens.
To really ensure that we leverage our commercial footprint across market archetypes and channels to ensure once we launch, we launch successfully. Third comes in the technical lens, which is incredibly important. Don't forget that we are selecting assets for development eight to ten years in advance of LOE, which means we need to ensure a product with a very strong product profile. And Claire and myself are going to provide you a couple of examples on what this actually means for Sandoz. Last but not least, while we want to leverage in-house strengths and capabilities, we will always explore opportunities for strategic partnership when and where it makes sense. This actually framework has delivered a broad and deep industry-leading pipeline, and this is true for generics and biosimilars.
Looking at generics, they will remain core for Sandoz, with over 450 products in the pipeline across many therapeutic areas and a very strong LOE coverage. Generics provide us scale in the market with very limited capital employment, deployment, and stable cash flow generation. In the midterm, we see increasing value coming from complex injectables and new emerging technologies such as GLP-1s. If you look now at the biosimilar part, we do have here again, a big and large growth opportunity, and we have tripled our pipeline in the last six years. What you can see here is 25 assets in the pipeline, focusing on major upcoming LOEs and really prioritizing where we can be first to market or where we can also have exclusivities with synergies in our commercial, manufacturing, or development platform.
The 55% is actually a really strong number, considering the real capital and financial investment needed to develop a biosimilar. We will, of course, look to add additional assets in the biosimilar space, but also explore new emerging technologies such as ADCs. So let me now deep dive a bit more into our biosimilar capabilities and pipeline, and then provide you also some color on how we're going to approach the sizable GLP-1 market. Biosimilars, a true success story for Sandoz. We're at global scale, the leading biosimilar company with eleven commercialized products. We annually are serving roughly one million of lives, and we have a proven track record in delivering on our pipeline with strong commercial capabilities and deep market knowledge.
In Europe, we're a clear market leader, and what you can see here also in the list of the products, we're leading in six out of 10 brands. In the U.S., and just outlined by Keren, we're actually leading three brands, and we have demonstrated successful launches in both the pharmacy benefit model and the medical benefit model, just recently in the pharmacy benefit model with the launch of Hyrimoz. Going to the midterm, and compared to the last five years, we see a potential in our plans to exceed 3 billion of fresh sales coming from launches, 50% roughly from biosimilars. And in this time period, we're looking at four key assets targeting roughly 30 billion of LOE value. Starting with Tyruko, as mentioned already by Keren, very unique asset.
We're the only and first biosimilar in the multiple sclerosis space, and we believe that we are gonna be the only one for quite some foreseeable future. We have launched successfully in Europe across key markets in Europe, with very positive customer feedback, and we're really proud to offer access for patients who are seeking more affordable options. Moving to Pyzchiva, which is a great example when was mentioning on partnership, where we have the ability to attract actually global leaders in biosimilars as our partners. In addition, of course, it leverages our strong position in immunology, and we do have a strong product profile, including all three strengths at launch. We have launched in Europe just recently, last month, and I would say so far the launch is really on track and the product is truly well received. Now, why is denosumab exciting?
Because we have two indications, osteoporosis and oncology, and we do have an industry-leading program. We have been the first one to complete the clinical trials and also filing in key markets. We have obtained regulatory approval already in Europe and in the U.S., and we have launched just recently as the first company in Canada. So finishing with Enzeevu, I think it's exciting because it has really sizable LOE opportunity in the ophthalmology market, which is still growing. Another great example on how we integrate early commercial insights into our product profile. We're gonna be the biosimilar with pre-filled syringes available at the time of launch. Why is it important? Because 80% of the originator Eylea is being sold in pre-filled syringes, and of course, this is key for our commercial success.
It also saves clinics time, and it increases the safety of the injection profile and process for patients. So moving to the long term, leading in terms of number of assets, but also the coverage of the LOE value in terms of originator sales, which is above CHF 160 billion. So we have 16 assets currently in early development, which means technical work or preclinical work. Two assets, pembrolizumab and nivolumab, we have entered into clinical phase, which we're extremely proud of. And as you can see, we're not gonna stop here. The plus means we're gonna continue to explore additional opportunities, including potential partnership, where we believe we add value, it adds scale, technology, and we can leverage our commercial infrastructure.
So now moving to the GLP-1 space, which, there's a lot of excitement that I think you read almost every day in the media. It is, of course, a huge opportunity, and it is expected to be a real growth catalyst in the generic space because it has a potential to reach over 100 billion patients across indications, and of course, a market which is huge and sizable, with what's expected to reach and exceed 150 billion by 2035. It's a very dynamic space, and the way we look at this market is actually in three phases. Phase number one is all about semaglutide and the launch into early market. We wanna leverage and maximize this opportunity with a planned launch of semaglutide in Canada as of 2026.
At the same time, of course, we wanna really leverage our technical and development capabilities and start to look into internal development of assets. We have signed a partnership for commercialization, which we're gonna use and benefit across the markets. Phase two, bringing the know-how of the early markets and the newly built capacity to expand the launch of semaglutide into major market like U.S. and Europe, while at the same time also looking and exploring newer opportunities like tirzepatide. Last, on the long term, of course, you know there are many molecules currently in development, and we're gonna explore the opportunities and reassess our pipeline as the market will evolve. Each of those opportunities, we're gonna always approach using a mix between internal capabilities, which we have in injectable space, and external partnership.
What do we need to do to make the GLP-1 space a success for Sandoz? How do we win in this space? Three main or core elements. First, and not different to what I have explained on the selection of our pipeline, we need to select the right product with a strong product profile and a program which is enabling us to launch and market formulation. Secondly, supply. GLP-1 is a lot about supply, and we're gonna need flexible, continuous, and competitive supply. Thirdly, we, of course, need to launch and want to launch with the right commercial model. So we're gonna look at this market. We're gonna see the market evolving and reassess our pipeline as the market is moving, and of course, also capital investment in line with the market evolution.
To close my part of the session, I would like you to leave with three takeaway messages. The first one is, we're in really strong position for industry leadership across generics and biosimilars, with an industry-leading pipeline, which is well set to deliver growth and favorable margin, while at the same time pioneering access to life-changing medicines for patients. Second, in the midterm, and compared to the last five years, we have a potential in our plan to exceed CHF 3 billion of fresh sales coming from launches, with an increased contribution from biosimilars. Last but not least, third, in the long term, we're looking to fully leverage our scale and strong LOE coverage in generics. We're gonna expand our pipeline in biosimilars, and we're gonna look for opportunities which make sense from a commercial perspective in new technologies such as GLP-1s.
With this, I'm gonna invite Claire, and I'm gonna hand over to Claire, who's gonna provide you more insights on how she and her teams are gonna support us in delivering the pipeline. Thank you.
Thank you, Rebecca. I'm immensely proud to lead the Sandoz Global Development Organization, and I think from all the presenters you've heard so far, I'm going to take a very similar format and talk about where we are today since we spun, what's happening in the near term in terms of progress through 2026 to 2028, and also looking at technology innovations from 2029 and beyond. Now, the Sandoz Global Development Organization is the engine that drives the commercial powerhouses that supply products to our patients in North America, Europe, and in the international market, and I'm immensely proud of all the products that we've already spoken about that have been launched, and those launches are only allowed or enabled because we've secured regulatory approvals of these key assets: denosumab, aflibercept, adalimumab, and natalizumab.
We've been successful with our development programs, our clinical programs, and our regulatory approaches to secure the approvals, and our commercial powerhouses have started to roll out the launches. In addition to that, we have also succeeded in achieving regulatory approval for over 130 products in the generic portfolio across a breadth of technologies to, again, show our development capabilities. Since spin, coming out of Novartis, we've been very focused on simplification of our processes and flexing our generic muscles and really developing increasing development agility as part and parcel of our strategy to ensure that we're able to bring products to market in the first wave after LOE expires or through competitive IP strategies. We have one of the broadest and deepest pipelines in industry, with over 450 molecules in generics and 25 biosimilars. That's the what.
I think the secret ingredient that we have is really the how. We have a strong development organization, and we are focused in the near term on ensuring that we have the right setup and capabilities to continue to deliver that pipeline, utilizing a combination of strategies around de-risking our portfolio through internal and external development, and really working with very good strategic partners, and also looking at how do we succeed in execution through a combination of having the right clinical approaches and also tapping into regulatory interfaces. As Keren spoke about AAM, we also have Medicines for Europe, working with those and other agencies to ensure that we are strengthening our regulatory interfaces. I want to take a few minutes. Rebecca spoke about us giving you some product examples.
We're very focused on the technologies, being very particular in the selection of our portfolio, focusing mainly on solid orals and injectables. And at the end of the day, biosimilars is a complex injectable. It ranges from having a small molecule API to having a large molecule API, which is what a biosimilar is. So we have the same platform. It's an API formulated as a solution or a suspension, presented in a vial or a device. So there are synergistic capabilities across complex injectables and the biosimilars. And the way that we have been able to succeed in getting these products approved through the regulatory pathways is through having strength in API and final dosage form characterization and development.
An example here, which you will see on the table outside, and I ask you to take time to look at the samples that we've provided for you. Ferumoxytol and ferric carboxymaltose are examples where we have succeeded in getting those products approved and to market, and they share very similar requirements in terms of proof of safety, efficacy, and quality with our biosimilar portfolio. The execution of immunogenicity and efficacious clinical studies, and I'm particularly proud of having pembrolizumab and nivolumab in phase one and phase three studies at the moment, already having demonstrated technical proof of similarity to the brand product. Working very closely with both the EMA and the FDA to ensure that we align on our regulatory packages, and we have a competitive position to get those regulatory products approved through that pathway.
And again, a similar platform for all of our injectables, whether it is simple, complex, or biosimilars, is our device capability. We have invested significantly in showing that we have the device development capability, and there was a question about devices earlier. We acquired a device company, Coalesce, in 2021, with a range of device engineers who have the technical capabilities and know-how and experience of successfully bringing products to market, and they are our interfaces with our external partners who provide us the devices. Having left Novartis, we needed to build our own internal technical development organization for biosimilars. We left with the project management organization, regulatory and clinical capabilities, and the early analytical capabilities.
But the technical development capabilities to do the early work and to do the formulation activities are something that we are investing in building, as well as investing in building our own manufacturing capabilities in Lendava, Slovenia. Because we want to have end-to-end vertical integration in the space of biosimilars, because that is an area where we want to continue to have industry leadership. So in parallel with building our capabilities in devices in Holzkirchen and Ljubljana, we will have end-to-end capability to do all aspects to demonstrate that we can, and have, successfully brought these products to market. As I said earlier, with the broadest and deepest pipeline in industry, over four hundred and fifty generics and twenty-five biosimilars, it is impractical to expect that we can do everything in-house.
That will never happen. The technologies are too broad. They are one-off technologies, which does not make sense to internalize.
So we're very clear on our portfolio selection strategy. We're very clear on where we play or where we don't play, and we're very clear on where we invest internally or we don't invest, and we also are very structured through identifying the right strategic partners, with Sandoz being a very attractive partner, as Keren already mentioned, for Samsung to come to us with the Pyzchiva opportunity. We're attractive because of our commercial excellence and ability to bring products to market, our development, regulatory, and clinical knowledge, which helps our partners to successfully bring products through, and we also are able to provide scale and de-risk development programs and show success. So some of the examples, as I've already said, Pyzchiva with Samsung is a good example. Natalizumab with Polpharma.
And I want to take a little bit of time to talk through Just - Evotec, because there was a question that Richard took and directed my way on the continuous manufacturing technology, which I think is where we are using strategic partnerships to access technology, not just products, but also technology. Currently, the technology platform for bringing biosimilar API to market is through fed-batch technology. The API is cultivated, it's then purified, and then it's actually collected. That's done in discrete steps with significant level of resources at each step. We're working with Just - Evotec, who have patented continuous manufacturing technology for the manufacturing of API, biosimilar API. A continuous process which they run over extended time, so it's actually called scale-on, where you use time as a scaling factor rather than volume as your scale-up factor.
Instead of going from 10 kg to 500 kg, you're multiplying your time to give you volume of API as required. This brings significant benefit in terms of yield, purity, volume, and it de-risk any profile changes in the API from scaling up from clinical to commercial. This really shapes the future of biosimilars using this continuous manufacturing platform, because it allows us to more efficiently manage future costs of goods opportunities. That partnership with Just - Evotec, as we've already spoken, is going particularly well, where we have some of our early development aspects, projects, in development with them. This gives us the opportunity today to continue with fed-batch, but in the future, to move to fed-batch and continuous manufacturing as needed. We've already spoken about our analytical and formulation capability, our drug device capability, regulatory and clinical expertise.
And as we look 2029 and beyond, where we are actually selecting products now that we will be developing and filing in the future, we see an increasing wave of products in the antibody-drug conjugate space, ADCs, and in the oligonucleotide space. I'm particularly excited about the ADCs, because I think the fact that we have excellence in small molecule development and biosimilar development, bringing the two together sets a great platform for us to succeed in the antibody drug conjugate space, where you add a small molecule through a linker onto the antibody. Similarly, with oligonucleotide, again, a complex API in a solution, in a vial or a device, we have demonstrated the capability to develop and manufacture those products successfully. So again, tapping into what we already know as a platform and as a foundation to secure the future.
So, I'm very confident that as the commercial opportunities for these technologies increase, and, you know, we work on selecting the right products, we have what's required to bring them successfully to market. So, I hope that gave you a little bit of the flavor of the what. What's the science that takes place behind the products that you see being launched successfully to give our patients access for medicines? We have a large and increasing LOE opportunity across both generics and biosimilars. We have a strong pipeline that we will deliver through a combination of internal and external partnerships. We have the internal capability to go into new technologies, and we have the network of partners, both internal and external, to ensure that we can successfully launch these opportunities. So, with that, I'd like to welcome Richard back, and we would open for the next Q&A.
Yeah, yeah. We're just gonna just give us, like, two minutes here to pull some chairs up on stage, and then we're gonna do about thirty minutes of open Q&A on any topic that you would like.
Bring your own chair.
You can bring a chair.
We're a purpose company. We bring our own chairs. We just need four. I think we're good, Rebecca.
I'm good.
Yeah.
Good.
Thank you.
So again, similar format. If you could just get the microphone, and then, obviously, all the difficult questions I can now pass to my colleagues. I don't have to answer them, so it makes life, my life a lot easier. Okay?
Carry on the GLP-1. Bank of America just want to carry on GLP-1, given that we've. Give a little bit more detail on that. Just when you're thinking about scale, the size and scale of that market, are you thinking that Sandoz will be scaling for a part share of the market? And so if you think about longer term, you factoring in fragmentation of the market across multiple new products like CagriSema, the GLP-1s, or are you thinking of this total market opportunity, the $150 billion that's in consensus as something to go after there? And on the LOEs for U.S., Europe, you said 2031-2035.
I think the patents are 31 Europe, 32 U.S., so are you factoring in there some additional flex for patent litigation to see a later launch, perhaps in the U.S.? Then when would you need to scale CapEx for those launches? Roughly, sort of, are we talking billions, or are we talking hundreds of millions of CapEx that you think you're gonna need for those? Thank you.
And I think, look, at the end of the day, this is a huge market. I think you'll be arrogant and naive to think that as a single company, we would take all of that market. So, you know, I think many players will enter that market, or a number of players. I think you'll end up like biosimilars, core of companies that have the capabilities. I think I agree with you. Look, I think that's why I think this is in a number of phases. This is a 10-15-year journey. I know everyone's sort of super excited or worried about billions of dollars of CapEx. I don't see it like that. You know, I think clearly we've got the early wave, the Canada's, the emerging markets will think about how that evolves.
Honestly, your guess is as good as mine about how that's going to evolve. So I, I see this almost as a laboratory. I think you're right. I think the U.S., clearly, the originators are going to do everything in their power to make this as painful for us as possible. You know, that's, that's this business. We know we're going to have a patent dance. So I actually think I think Europe, now this is my conjecture, I think Europe will probably fall before the U.S., but who knows? I think clearly we'll have to go through that process. And then beyond that, you look at things like tirzepatide. In terms of CapEx, at the end of day, we're an injectable company, as Claire and Rebecca have talked to you about, you know, most of our assets.
So really, it's about investing in injectable capacity, which is multi-use. So I see this more in the hundreds of millions of dollars incrementally over a period of time, coupled with partners, rather than billions of dollars, because we're not an API company. Yeah, sure, we want to be an API business in biosimilars, but we're not an API company in terms of particularly GL. These are chemically synthesized generally. You know, there are plenty of API suppliers developing product. What we're good at is take an API, a device, a regulatory package, getting it approved, and then fighting in court. That's what we're good at. So we'll play to our strengths, and we're not in the business of chemical synthesis. Okay.
Thank you. Good afternoon. Florence Cespedes from Bernstein. As surprise, surprise, a follow-up question on GLP-1s. For the first wave, 2026 in Canada, is it fair to assume or will you also try to develop the oral formulation, the Rybelsus product, because they have a specific technology, and that... Or will you target the injectable form first? Is that my first question. And then the second question on natalizumab in the U.S., could you maybe give a little bit more color about the delay on the JCV assay that you are developing? 2025 means, beginning of the year, end of the year, and what is behind this delay? Thank you.
Okay, so Rebecca, do you want to explain why we're not into value-added medicines? And, Keren , I'll let you pick up on natalizumab.
Now, listen, we currently see in the market eight assets in GLP-1, right? And we're covering six already of those eight, and we're gonna look to add as the market is evolving, right? I mean, one you are saying is an oral formulation, and we need to see how this is going to pick up and depending on market, so we see some markets where this is a success, others less, so we're going to discuss this internally, whether this is an asset we want to invest. What I can tell you today, definitely, semaglutide is a big opportunity, and we really want to focus now on the launch and ensuring that we are at stage when the market is really opening up in Canada as of 2026.
Regarding the JCV assay, the reason that we didn't give you a more specific date is that we just got, honestly, the questions from the FDA. So we are working to assess and to understand what does it exactly mean. We anticipate that given every interaction with the FDA takes time, 2024 will be a stretch, but we're really assessing now when in 2025 we will be able to launch.
Hi, Emily Field from Barclays. And just a confirmatory question on Tyruko. I'm assuming that this potential delay has no impact to 2024 financial guidance. And then two other questions. One, just on the 4% U.S. generics growth rate. You know, obviously, we're all asking tons of questions on go-forward price deflation. I was just wondering if you could give any thoughts on how that 4% breaks down into volume and price. And then, on when considering the development of a biosimilar and, you know, in the presentation you were segmenting between the pharmacy benefit and the medical benefit, how big of a consideration is that when you're considering development in terms of the channel and reimbursement that the product is sold in?
Or is this, you know, sort of size of the product and potential competition more of a factor? 'Cause that's just something we weren't totally sure about. Thank you.
Chris, if I take the first and the last, and then, Keren, I'll let you talk about pricing. No, it does. I mean, it was always going to be a relatively modest launch this year, so it doesn't change our guidance for this year. In terms of selection, I think we said earlier, and Rebecca reiterated, we're a European company. We choose our portfolio nine years out sometimes. It would be impossible to think about an individual market. So we focus on, can we get our value back from a European investment? And I think, as I said, we see then the U.S. as an opportunity, so it's incremental. We have no strategy to say, well, we prefer PBM to hospital benefit or, sorry, pharmacy benefit to hospital benefit. I think that would be completely the wrong way to think about it.
It's very much Europe, and then we leverage the infrastructure and capability and launch in the U.S. Now, inherently, immunology generally is more towards a pharmacy benefit product. Oncology and other products tend to be more medical generally, but that's more just as it is, not through any strategic thought process or imperative. Keren, do you want to talk about the U.S. pricing?
Yeah. So we don't guide for a specific, you know, price erosion per market, but I would say that we assume that what we see now is what we're going to see for the rest of the year. I would say, you know, I always say that price erosion, you know, the market is not erode, it's specific products. And if you look at our portfolio, it's very mature portfolio. So to some extent, a lot of the products, as I mentioned, prices are too low. There is not a lot of room to move anymore. So we anticipate that what you see so far in the U.S. for this year will remain the same.
Thank you. James from JPMorgan. Moving on from GLP-1s, ADCs, I saw was on the slides, and $32 billion target, was it from 2029 to 2034? But how much more difficult and how much more expensive do you think it's going to be to develop a biosimilar ADC? 'Cause I know even some of the innovator companies have found the linker is a bit fiddly and some other aspects complicated. So is it that you might just do, like, one or two of them because they're going to be more expensive and more challenging, or are you going to go after most ADCs because it's, it's going to be straightforward? And are these very far off? They're like the wave beyond GLP-1s, these get interesting, or could you actually launch something in 2025, in 2029 or 2030?
Claire, I think that's a good technical question for you.
Thank you for the question. It is more challenging because you're adding a small molecule through a linker onto the monoclonal antibody, and so the manufacturing challenges, I think, are quite significant, and there are some HSE and toxicity considerations that need to be taken into account. From a timing point of view, it takes six to eight years, typically, to develop a biosimilar, so even if we were to start tomorrow, we won't be able to launch in 2029, so I think you're looking at 2030 and beyond in terms of coming to market with one of the ADCs, and I think our approach, our very rigorous and disciplined approach in selecting the portfolio will define which particular assets we would go after.
But also one of our strengths. I mean, at the end of the day, we're a small molecule company, and we're a monoclonal company. So actually, this is actually a good example where those two things actually create a beneficial synergy between those two things. And also, our partnership with Evotec allows us potentially as a development and manufacturing platform as well. So-
Yeah.
It's sort of a nice way, but it's actually one of our moats, our strength in terms of the development organization, this capability to combine large molecular science and small molecular chemistry.
Thank you. Two other ones, please. One was on Humira in the North American business. So it's done very well with CVS, but have you effectively hit a ceiling in terms of how much this product can do? Now, the only way is down in terms of pricing. So does it become a headwind we need to start worrying about for next year, or can there still be some more growth there?
Keren, before we get into budget discussions.
I thought you had a question on ustekinumab.
That's my third one.
Yeah, no. So I would say with CVS, we probably achieved kind of where we can get because, as CVS, kind of, Cordavis announced, they reach more than 90%, kind of, you know. So we looked at the commercial business. If you look at the commercial business, where we were the only one on formulary, probably that's more or less the kind of the volume that we would see.
Don't forget that other kind of PBMs didn't displace yet Humira. One example is ESI. So they did announce, Cigna did announce just recently, last week, I think, that they will have private label through their Quallent business with BI and Teva, but they did keep us on formulary with our adalimumab-a daz. So definitely we do think there is more opportunities. The question repricing, honestly, it's very hard to predict. It's a very competitive market. So I think from a share perspective, there is definitely room to grow. From a price perspective, it's very dynamic.
Thank you. And I think you sort of preempted my third question, which was the question I asked before. So is how you've done with Humira a precedent for how you might do with Stelara, and could you do a CVS-like deal, or is this a smaller opportunity? It's not something to be as excited about for twenty-five.
So I would say that, it's fair to assume as a market, not specifically as Sandoz, that the market will follow the same approach. As I mentioned, we did see other kind of PBMs taking the approach of a private label. Specifically for us, it's too early for us to share our commercial kind of plans for next year.
Thank you.
One at the back. Thank you. Folashade from Redburn Atlantic. Just two questions from me. So the development work you did for Humira, the Humira biosimilar, only involved one indication, while the work for the Keytruda biosimilar involved non-small cell lung cancer and melanoma. So was this due to a regulatory or more of a commercial decision? And the second question was, the combined enrollment of these was also higher than for Hyrimoz. So is this due to evolving regulatory requirements, or if you can elaborate on that, that would be really helpful. Didn't hear her question.
Claire? I think the complexity of, I guess, the relative cost or complexity of developing a Keytruda versus a Hyrimoz. Is that the root of the basic question?
Okay. So I think the first question was around whether it was a regulatory or commercial decision. It was actually a commercial decision. I think the development pathway for the development of these molecules are very comparable. In terms of the question between the cost and development of the two different aspects is actually the biggest consideration in development of the biosimilar is actually the clinical costs. And we work really closely with the regulatory agencies, depending on the indications, to ensure that we design the right clinical programs, and that's where you have the flex in terms of the size and scale of the regulatory challenge and the commercial challenge on developing the assets.
But a drug like Keytruda-
But again-
You've got to get samples.
But a drug like-
You've got to spend a fortune on samples to cover the indication.
Yes.
I mean-
The most expensive aspect, as Richard said, is actually securing the reference-listed drug against which to do your clinical studies. So all of those are taken into consideration when we value the asset, first of all, to decide if we're adding it into the portfolio, and then pretty much the development journey and the regulatory journey are comparable. And again, you know, as I spoke about, we have proven capabilities in succeeding in, in those spaces.
Thank you.
Thank you.
Brilliant. Thanks. Harry Sephton from UBS. Just one on biosimilar aflibercept. So in the European market. So I think we understand your acquisition of Cimerli in the U.S., wanting to get more exposure to the ophthalmologist market. But in Europe, if I think about how this market is split up, you have very cheap compounded Avastin, and then you have, I guess, ophthalmologists, which have the more novel therapeutics coming out, like Vabysmo and high-dose Eylea. I guess once you have a biosimilar Eylea, it kind of fits somewhere in the middle between them. So how is the ophthalmologist market split up in Europe? And so, you know, what is the addressable market between those who are very price sensitive, already using compounded Avastin, and those who are less price sensitive and are want to get the highest efficacy?
I'll let Rebecca answer in her capacity in her old job.
Exactly, in the new. The way we look at this market, and this is a bit true for, in general, the biosimilar market, is you have the existing market, right? So what is existing there, and then you would expect that there's a big remaining part now moving to high-dose concentration. So we see this across different products, that it not all the patients are going to move, depending on the market, depending on reimbursement, depending on price sensitivity, as you just rightly said. And then don't forget, there is always an additional part, which is actually the attractive part, but there is also market expansion, right? So once you have a biosimilar, you may use even more of aflibercept because it is more affordable. So you will see also the expansion of the market.
So that's why I would not just focus simply on saying this is a EUR 4 billion opportunity in Europe, which it actually is. So you need to consider that it has volume expansion, but of course, there's going to be some transition to high-dose concentration. The exact part and percentage, I think we need to see how the launch is now going to evolve with the high-dose concentration.
[Emmanuel Babalola, X TV]. Interesting to see you put up the comment about oligos. Could you just talk a little bit about what opportunities you're focused on? Is it just therapeutics or also potentially oligo-based vaccines, and maybe some specifics in terms of projects, timelines, and what do you think the regulatory requirements look like on both sides?
We're not a vaccines company.
Okay, understood.
... Is there anything to add to that, Claire?
No.
Rebecca? We're not a vaccines company, but we're talking about oligonucleotides.
No, the question was on oligonucleotides.
You're asking us strategic direction. What about therapeutics then?
Again, we wouldn't. I mean, I think we need to evaluate. I mean, these, a lot of these are orphan drugs, are very niche, so it's really where we see either potential that we could massively expand the market. There's little point to launching products in very, very tiny indications unless we think by bringing it, we can bring the price points down and expand the market. I would apply the same logic to things like cell and gene. There's no technical reason why we couldn't potentially invest and do that, but even if we could bring cell and gene at $100,000 a patient, I don't think there's enough addressable market to recover the investment. So, you know, and at the end of the day, there is a significant amount of portfolio.
There's something like 45 biosimilars or biologics with no biosimilar development pathway that we see. So there is a very broad opportunity in terms of both basic monoclonals, ADCs, and then also potentially targeted oligonucleotides.
Yeah. And maybe just building on what you said, and this was one of the main messages we wanted to bring across. If you look at the slide with the LOE landscape, actually, the biosimilar, the pure biosimilars, not the oligonucleotide, which was a smaller piece on the twenty thirty-five horizon, is still a huge opportunity, right? I mean, it's going to almost double over the next five to ten years. I think we're going to have massive opportunities just by launching biosimilars and oligonucleotide. We're also going to, of course, explore, but we first need to understand how the market is going to evolve and then maybe also look for partnership, right? So we said we're always going to look for how do we leverage internal capabilities, and then how do we explore also partnership.
I could imagine that oligonucleotide could be one area where we want to go for partnerships.
Thank you. So just to be clear, it sounds like that's a more hypothetical long-term future opportunity rather than ADCs, for example.
I guess it's in the value evaluation-
It's a long run.
At the end of the day, I want to be clear about what we don't do as much as what we do do. Clearly, we're already a strong leader in biosimilars, in monoclonals. That's a space with significant opportunity to expand and grow. So ultimately, we have to I want to own a lot of that space and bring as much portfolio. And then there's other products on the periphery, whether it's, you know, oligonucleotides or other therapeutic categories. Clearly, GLPs, you know, are a unique category. We think we're well positioned, but I think our main focus is going to be monoclonals.
Mm-hmm.
That's really what the space that we really need to own.
Thank you.
Hi, it's James Vane-Tempest from Jefferies. Thanks for taking my questions. I've got two. Perhaps if I can start coming back to my biosimilars question from the prior session. I understand from your answer to James's question, pricing with PBMs is dynamic, but when are these contracts expected to be renewed? And if any renegotiations come with price cuts, given your significant volumes, how dynamic is your cost base to absorb that, to maintain margins, and what will be the potential risk to your longer-term margin target? And I've got a follow-up. Thank you.
Keren?
Just to make sure, you are referring to Cordavis? Okay. Yeah, so as we shared in the beginning, this kind of a agreement was a long-term agreement. It was not what, just one kind of a year agreement. So we are set kind of for more than one year. I don't want to give any additional commercial details about this arrangement, but I want to make it clear that it was beyond one-year arrangement. And I would add that Cordavis is also very happy with the partnership and, you know, the success that we had in the market. So, we're working closely to make sure it's continued to be a successful story for both company.
But at the end of the day, it's just a component part. I mean, I think as Keren said, ex-Cordavis, we're still the number one biosimilar adalimumab in the market, and I think it's huge. I mean, you've seen still 80% of the market to go at. So even if that stabilizes and potentially comes down a little bit, I think then you'll see incremental growth, not step growth, in our own label product. I think we're still on formulary with all the other PBMs at the moment. So I think we're well positioned. And then let's take a step back. Why? Okay, ex-US, we're the world's biggest supplier of biosimilar adalimumab. We have a good cost of goods. We're vertically integrated. We have a great device. In the US, we're the only company with a starter pack.
We have a patient support network. So I think we've built a whole ecosystem around this product that a lot of our competitors just haven't. They've seen this more transactionally. We've invested. I think one of the best compliments I got was from one of the partners. They said, "Look, we've really enjoyed working with you because you're all in. You're all in into biosimilars. This is your strategy. You have to succeed." And, and I think that's played out extremely well in the U.S.
And just to add, you know, when Richard talked about a device, and I hope you had an opportunity. It's the best device out there. I was in the field last week, and I had one of the nurses coming with, like, eight devices, and she said, "I love yours the most." And she showed me how easy it is to show to patients how to use it. You know, it's usually RA patients. It's really hard for them to hold the device. So I do think, again, we keep saying that biosimilar, you know, you don't have differentiation, but there are elements of the product that make a difference, and this is a big one.
Yeah, I would urge you to have a look at that. I mean, the fentanyl, unfortunately, is only a placebo, but...
Thank you. My follow-up question was the 25 products in the pipeline. I know you tend to only give visibility when you get to sort of phase III, but I guess you've obviously got a lot of launches kind of coming up, but when are we likely to get more color with what's coming down the pipe?
As they get to phase III. Because again, you know-
But can we expect, like, you know, any, any couple of products, you know, this year, sort of, you know, in terms of, that you might be able to tell us might be getting to that stage? Or is it... I'm just trying to understand the depth of the twenty-five. You know, is this, you know, are we likely be seeing, like, three to five years, or could be something else kind of be announced this year? Not any indication of what they are, but just in terms of the numbers which you might potentially have coming down the line.
... when we-
Listen, but I can give you a bit more color. Let me give you a bit more color. So in terms of names, we're really gonna follow the phase three, because this is publicly available. So yeah, anyway, gonna know what we have in clinical phase. But what I can tell you, out of the twenty-five, the biggest part is gonna go again into oncology. It's gonna help you, right? Because you can see the LOE landscape and immunology and of that, right? So even in the future, we're gonna have a big part of the twenty-five assets, which gonna come again on our commercial infrastructure, which is actually, I would say, the great news we have. And then we're gonna add assets, which I was showing with the plus, of course, building then on our commercial infrastructure.
We're gonna provide you the name as we are moving into clinical phase, but a big portion, oncology, immunology.
That's great. Thank you.
Hi, I'm Emily Field from Barclays. Kind of a follow-up to some of the questions asked earlier. I mean, you mentioned the high reference price of Keytruda as being a factor under consideration, and then some of these other biologics as not necessarily having a pathway for biosimilar development. I was just wondering if, you know, some of these orphan drugs that are still early in their branded life cycles, such as Vyvgart or Ultomiris, I know you won't be at the Soliris biosimilar. You know, are these products with very high reference prices, but also potentially very high branded sales, ones that would be under consideration for development?
Highly unlikely. They're not an orphan drug. I mean, again, unless. You know, the whole point is about patient access. Unless we can bring a product to the market, whereby bringing the price down, you massively expand it. That's why I'm so excited about denosumab, because clearly, if you think about the breast, the, osteoporosis indication, at the moment, it's either that or bisphosphonates, you know, basically radiator fluid. So here the opportunity is to offer patients a much better treatment protocol, potentially. So that's the opportunity to grow over many years. But so really, there's a lot of other assets that I would prioritize ahead of that.
Mm-hmm.
Hi, Nicolas Poyade from Kepler Cheuvreux. So maybe to bounce back on the pipeline question. So you will launch the Eylea biosimilar, let's say, worst case, 2026, and you have these two products that are already in clinical study, but that will come to market around 2028 at best. So are we supposed to expect that you will have some licensing to fill this gap, as we move forward?
We wouldn't comment, and I can't comment on the launch timelines of... I mean, clearly, Europe is one timeline, and then the US is a different timeline for aflibercept, so we'll see how it evolves. But I mean, clearly, in the US, we already now have one product. If we can find other opportunities to leverage that, so long as it's attractive in, on strategy and accretive, then we would look at it.
Thanks. Graham Parry, Bank of America. Just on adalimumab, what do you think it is gonna take to expand the the biosimilar penetration overall? Obviously, you're doing incredibly well in terms of share within biosimilars, but 19% is perhaps less than we'd seen by similar biosimilar penetrations, for particularly the medical benefit ones. So just help us understand how you get about the overall market penetration increasing there. And then secondly, we haven't really asked much about Europe, which is half your business. So just any political regulatory concerns that you have over Europe at the moment? There's obviously, you know, the politics of Europe is shifting. So strategically over time, how are you defending yourself against, you know, perhaps more protectionist or more nationalistic trends across Europe?
Okay. Okay. Keren, do you want the first one, and Rebecca, in your own job, you can answer the second part.
Yes. So my short answer would be that we need more PBMs to displace Humira from formulary. Now we saw only CVS doing it. You will see much broader biosimilar access once others will do it. As I mentioned, Cigna already ESI said that they will do it for some of their plans in 2025 , so we don't know which are the specific ones, and I assume we will hear more kind of updates from the others as we get closer to 2025 . But by displacing Humira, the challenge that you have is, as you remember, all the PBM put the biosimilar at the same kind of position, at formulary position, so we were all preferred.
So if the physician does not need to switch a patient, if it's all at the same kind of category, they will not do it until they don't have a choice. So that's the difference. So I think with new patients, when you talk to the physicians, they understand that it's coming, and they prefer to start many of them on the biosimilar rather than start and change. But for the existing patient population, really, what will change the share, which is most of the, honestly, patients on this drug, will be more access through the PBMs.
Rebe-
Yeah, let me maybe start with what we have been pleased with. So currently, it's still in discussion. We're still in discussion. No, but the part I'm pleased is actually that we have broad alignment on the Bolar exemption. So we do not expect major changes when it comes to patent protection in Europe in the future. And this is a good news for us, and I think it's absolute giving us stability and predictability, which is really needed if you play in this market. Where I have concerns, actually, is that we see more and more regulations which are trying to solve a problem with more policies rather than giving up flexibility. I tell you what I mean.
So if Germany starts to implement the six months of stock, safety stock requirement, this means that 25% of our total supply, if you take the example of anti-infectives, is actually in Germany. If you would add France with the same example, you go up to 50% of our total supply being in two markets in Europe, which means actually you're left-
... out, Central Eastern Europe. So there I'm really concerned, because what we need to ensure supply and access to medicines is more flexibility so that we can shift products across markets with harmonized products, and I would say less regulation, because patients would definitely benefit from this trend and direction. So this is my biggest concern.
But I think, look, ultimately, most of most European governments see us as part of the solution, not part of the problem, so I think we have an extremely good voice. One of the benefits, I think, being as an independent company, Keren and I, and Ingrid had the pleasure to go to the White House, to the FTC, to Congress, we had dinner with the head of the FDA. We have great access. People want to talk to us. We didn't pay for any of that access. And so I think we have a really unique voice, and one of the things that I'm really proud of is our ability. You know, Rebecca was president of Medicines for Europe. Keren is president of the Association for Accessible Medicines.
So we have a really strong voice that we would never allowed to have while we were with our parents. So I think that we, we're trying to leverage more and more, and I think it presents an opportunity. And given that we are basically a European bi- you know, generics and biosimilar company, I think we're well positioned. We're the only antibiotics manufacturer left in the Western world. You know, that's your choice. It's either us or China. That's the choice for basic antibiotics. So it gives us a very, very powerful voice. Okay, I think with that, thank you so much for all of your questions. A really good... Hopefully, a useful session for all of us. I think Remco just wants to say a couple of words. Don't get too nervous.
Yes.
It's okay.
Thank you. Thank you very much. Perhaps if... Keren, can I ask you to-
Yeah, yeah, yeah.
Come on stage? As you know, unfortunately, Keren has decided to leave us. Please come on stage. No, no, no. I have to tell a few words about you, correct? She has decided to go back to the United States. She found another job. She thinks it's a better job. I'm still dreaming that in a month or two, she changes her mind and comes back. But for the moment, she decided to find a job closer to home. She's commuting between the US, here, and Basel. This is actually her last week. So I thought that would be probably the best moment in front of you, the analysts and investors. Thank you very, very much for the work you've done.
I, unfortunately, had only the privilege to work with her over the last two months, but I think many of you worked close with her, and all the feedback which I've gotten from you is that she's done a really, really good job also by helping the spin-off, correct, and all the work you have done over the almost a year together with. So I wanted to thank you very, very much for the work you have been doing, give you a little present so you don't, you don't forget us, correct?
Thank you.
Yeah.
Thank you so much. I think drinks and a small cocktail reception is next door, so happy to continue the conversation there, and thank you again for your questions and participation today, and thank you for taking the trouble to give us your time.