Good morning, everybody. Welcome to the Sandoz Capital Markets Day. What I wanted to say is a big thank you to all of those people who've actually managed to get here. We've had a number of people who've actually had to cancel because of their flights and things like that, because of the New York-related issues with the weather and the smog. For all of those who've made it here, congratulations getting to the place. It's wonderful to see you all. If we just go through... We've got a packed agenda, and it's on slide four for the people who are on the webcast. We've divided the day into four main areas. Initially, we're going to go through the Sandoz business, the strategy, investment proposition, which is going to be led by Gilbert, the Chairman-Designate, as well as Richard, the CEO of Sandoz.
We then go through into the commercial section, which is our session two, and you'll hear from the heads of the commercial parts of the business across the three regions for Sandoz. Following that, in the afternoon, we're gonna go into the operations part of the presentation, and finally, we'll finish off with the financial outlook and the overall wrap-up of the day and with the key messages, et cetera. One thing to emphasize is there's gonna be plenty of time for Q&As at the end of each session. Today's objectives for the Capital Markets Day is obviously, people are here from Sandoz Management, so you have an opportunity to actually meet them. We're gonna introduce you to the Sandoz, the company, its strategy, the growth drivers. We're gonna explain the benefits of Sandoz as a standalone company, as opposed to being a part of Novartis.
We're gonna go through the financial framework as well as the guidance to midterm, and of course, we'd like to answer any of your questions. Now, couple of things just to bear in mind. The first one is the Sandoz spin is still subject to Novartis Board of Directors approval, and subsequent to that, it's got to go through the shareholder vote, and we're planning to do that at the extraordinary general meeting. Besides that, and before I hand across to Gilbert, who will introduce some of the management, I just wanted to read the safe harbor statement. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties, and other factors. These may cause actual results to be materially different for any future results, performance, or achievements expressed or implied by such statements.
For a description of some of these factors, please refer to the company's Form 20-F and its most recent quarterly results on Form 6-K that respectively were filed with and furnished to the US Securities and Exchange Commission. These are the presenters, and I think Richard is going to spend a bit more time actually going through. It's my great pleasure to now introduce Gilbert Ghostine, the chairman designate. Gilbert?
Good morning, everyone. Thanks, Samir, for your introduction. We are all extremely excited to be here today. You know, this morning, you know, this is our First Capital Market Day for Sandoz. It's a very important day, very, very memorable event. At the same time, you know, Richard and I and the executive committee are extremely excited to share with you our passion for this business. Although, as Samir said, there is fog outside, you know, we will give you very good clarity into why we're excited about this business and what will be the key milestones that, you know, we will deliver against between now and 2028.
My name is Gilbert Ghostine, and I'm extremely excited to be to have been and honored to have been appointed by Novartis as the chairman designate for Sandoz during this very important transition for this business. We will share with you some deep insights into, you know, what makes, you know, Sandoz a really European champion and at the same time, a global leader in the world of genetics and biosimilars. We are extremely proud of our past, but at the same time, you know, we are extremely excited about the future because, you know, we will share with you later on, you know, why we're excited and what are the opportunities and milestones that we have ahead of us.
I joined Sandoz in February of this year and immediately have been extremely impressed by the quality of our team, the entrepreneurial culture, and at the same time, you know, how proud and excited are our people to be able to shaping healthcare and to make a difference to society. The reason I was extremely excited to join this company is this mission. You know, when we are thinking about, you know, bringing affordable medicine to underserved population, and at the same time, you know, all of this coupled with the exciting value creation opportunity for our shareholders and key stakeholders. Turning to Sandoz, the uniqueness of this brand starts with its name and its roots. You know, Sandoz is not only recognized in its home market, that is Switzerland, but all around the world.
The recognition and the credibility that the brand has is mainly driven by its commercial strength, at the same time, you know, by the credibility that it has built over time in the market with customers, with consumers, making a difference to society. At the same time, you know, making a difference and taking a leadership in everything related to off-patent medicine. This is a result of not only, you know, a long-standing Swiss heritage, but at the same time of a consistent commitment to its purpose of pioneering access for patients on a global scale. This, combined with a long and strong track record of high-quality delivery and reliability, as well as the ability to select first to market opportunities through constant innovation, will continue to make Sandoz a credible global brand that will stand out in this industry over time.
Sandoz has come a long way since its creation in Basel back in the late nineteenth century. You know, with innovation in its core, the company has a strong heritage in bringing life-saving medicines to patients. Sandoz was not only the first company to introduce oral penicillin in the early '50s, but most importantly, the first biosimilar in 2006. In 2005, Sandoz established its leadership position in the generics industry with the strategic acquisition of Hexal in Germany. It later became the first company to achieve blockbuster status or more than $1 billion in sales with a generic enoxaparin. In the last decade, Sandoz continued to strengthen its leadership in generics and biosimilars with targeted investments in biosimilar capabilities, combined with value-accretive M&A and strategic partnerships.
This contributed to the creation of the current strong and rich pipeline of more than 400 generics and 24 biosimilars, and one of the broadest generics product portfolio and a leadership position in biosimilar in six out of 10 of our big global markets globally. Our heritage sets a strong basis for future success. Deeply rooted in Basel, we announce our intention to keep our headquarters in this global life center and at the same time, that is ideally located for us to attract high-quality top talent. We will remain a key player in antibiotics and keep investing in the last vertically integrated antibiotics generics production in Europe to support increasing global demand. We will also continue to invest in capabilities that offers us the flexibility to develop new technologies and support our focus on first to market opportunities in complex generics and biosimilars and beyond.
With its leadership position in generics and biosimilar, Sandoz is at a very different point along the biopharma value chain compared to the innovative medicines business of Novartis. The limited synergies between the two businesses support the proposed spin-off, which offers numerous additional benefits. Enhanced focus with simplification and optimization of resources allocation to deliver on our ambitious objectives. Greater agility and freedom to operate and adapt to evolving off-patent medicine market conditions that will require lean and fast decision-making. Improved accountability with ambitious value creation goals and clearer business objectives as a standalone company, more aligned to the specificities of our industry. Value creation with a clear path for more profitable growth and enhanced shareholder returns. Our business is poised to grow in the midterm with significant margin improvement and free cash flow generation, as you saw this morning from our press release.
Last, a generics culture fostering an entrepreneurial and agile mindset with a drive for executional excellence. A spin-off will allow Sandoz to pursue its vision to become the world's leading and most valued generics and biosimilar company, and continue to create sustainable, long-term value creation for our shareholders, and a major impact for society. My first task as a chairman designate has been to set up the board of directors of standalone Sandoz. I'm pleased with the group of leaders we have put together, a truly world-class board at the level of Sandoz ambitions. The new board brings a broad range of expertise and capabilities to help Sandoz fulfill its value creation aspiration.
As you could see on the screen, in its 10 members are or have been active in some of the largest companies in healthcare and across a wide range of other industries, as board members or as executives. Sandoz board composition stands out, with 60% of its members being current or past CEOs or CFOs. 50% have deep healthcare expertise. 50% have strong experience and expertise in FMCGs. 40% are female, 100% are independent, and no over-boarding. The board of directors will have three subcommittees: an innovation, development, and science committee, a human capital and ESG committee, and an audit, risk, and compliance committee. We have started the preparatory work and will be effective following the planned spin-off of Sandoz in the second half of 2023. Obviously, as Samir mentioned, subject to Novartis' board of directors and shareholders approval.
I'm looking forward to working with the new board to help set up the strategic direction for Sandoz and support its future development. Before handing it over to Richard, I would like to express my appreciation for our fruitful collaboration over the past several months. Richard is a seasoned and proven CEO with a wealth of experience in the generics and biosimilars industry. Richard is someone that is truly passionate about this industry. He really cares. He wants to make a difference. He wants to make Sandoz a big success, and at the same time, he is really committed to shaping healthcare and giving access to clients, and a deal in a leadership position with off-patent medicine. Because of his in-depth expertise of this industry, he has been appointed as the chair of the International Generic and Biosimilar Medicines Association CEO's Advisory Committee.
Richard, since he was appointed as a CEO back in 2019, you know, has proven his capacity to transform this business, put around him an outstanding leadership team that you will have the opportunity to get exposed to later on, drive performance, and at the same time, create, through his relationship, a pipeline of innovation that can transform this business into the future. This is why we are extremely confident that we will be able to deliver against our ambitions. With this, I will hand it over to Richard. Richard, over to you.
Good morning, everybody. It's a pleasure to be here, and thank you for coming. Perhaps just a few words about myself, and then I'll take you through the rest of the presentation. Clearly, I'm British. I've been in the generics industry pretty much all my working life. This is actually the second time that I've been in Sandoz. I used to be here about eight, 10 years ago. In fact, I did Paco's job, and you'll hear from him a little later on, running the international markets. I then had a brief sabbatical and then came back four years ago, really to think about how we could really focus Sandoz as the world leading generics and biosimilar company. In many ways, Sandoz is truly a unique company, and that's very much what I'd like to take you through today.
Fundamentally, the most important thing to reflect is Sandoz is the only global generics and biosimilar company that actually wants to be a generics and biosimilar company. And that is core to our focus, core to our passion, core to our reason, and key to our future. I'd like to just perhaps take a little bit of time, take you through who we are as a company, the journey that we've been on over the last four years or so, and then critically, why Sandoz is such an attractive investment proposition. Really, Sandoz has one single purpose, pioneering access for patients. Our reach globally is just truly phenomenal. We serve over 500 million patients every year, and the social impact in terms of savings to healthcare systems and payer frameworks is nearly $200 billion.
It's an incredibly proud moment to be able to stand here. I want to explain to you the impact this company has, not just in Europe or the U.S., but globally. There's a lot of numbers on this slide. Really, what's key? The market that is, we operate is significantly large, about $200 billion. Our sales for 2022 were $9.1 billion. We have a European champion, strong in leadership in the majority of markets around Europe, and you'll hear from Rebecca a little later on about our incredible business there. We have a pipeline that I believe is unrivaled. Over 400 small molecules in development and 24 biosimilars, which is an industry-leading portfolio. We serve over 100 markets, and have an incredibly strong and diverse leadership team that is behind and supporting the growth of this business.
If we look at our business for last year, sales $9.1 billion, of which 79% were made up by generics, small molecule business growing at about 3%, we have at 9%, 21% of the biosimilar business growing at about 9%. It's worth noting that the biosimilar business consistently grows years after launch in a way that the small molecule business doesn't. It's also one of the broadest portfolios globally, we have launched 8 in-market biosimilars, again, a leading position. What's exciting is the increasing proportion of biosimilars of our business over time. Five years ago, it was about 15%, clearly, that proportion is accelerating with all the benefits in terms of growth and also in terms of margin expansion.
When you flip it and look at it by region, clearly, Europe is the foundation of Sandoz. 50% of our sales growing at 6% is our European business, covering nearly 40 markets. Again, strong position, one market's up and one market's down. We have a very strong, consistent business. Again, I'm delighted that Rebecca could take you through that. Paco has built a really focused, strong international business, serving about 50 markets globally, consistently growing, delivering about $2.5 billion of sales, and last year growing at 7%. Keren in the North America.
Probably the single biggest challenging element to the generics industry, Keren and team have done a phenomenal job stabilizing the business and now positioning our business to be accretive in terms of growth and margin as we bring a strong pipeline to the market over the coming years. That's a little bit of thought about the journey that we've been on, getting Sandoz back into sustainable growth. I guess, as any organization, we focused on our talent, thinking about how we've built a strong, capable leadership, either experts in their field or with deep experience in terms of this industry and the opportunities that it presents. We've aligned a long-term vision to become the most valued and valuable generics and biosimilar company in the world.
Focused ruthlessly on sales execution, at the same time, expanded our pipeline and improve on our launch performance, investing in capabilities, and forming strong strategic partnerships, both in development, supply, and commercial. You'll hear from many of my colleagues today, I have a team that has deep experience in the generics industry and are leaders in their field and capabilities. As a team, we all share the same passion in terms of delivering access to our patients. Ultimately, as I said, the beginning, we are proud to be generic, that's driven a mind shift culture in the organization, focusing on execution, entrepreneurial leadership, that's allowing us to attract talent and retain a strong employer brand. We celebrate empowerment and promote agility and accountability across the organization, all consistent to our vision to become the world's leading generics and biosimilar company.
We focus ruthlessly on sales execution. We've prioritized growth by expanding share and winning new products in new markets. We've invested in our pipeline, our capabilities, particularly in the U.S., and again, we'll spend more time reflecting on that today. We've executed targeted, accretive M&A and BD&L, and we've stopped doing anything that was non-core. The results have followed. We're now in the position that we've had six continuous quarters of growth. We've expanded our European leadership, taking share against most of our competitors, and accelerating our growth in international and stabilizing our U.S. business. There are a lot of numbers on this slide, but in many ways, this starts shaping where our future starts to come together. We expect to more than double the launch contribution sales from the pipeline that we intend to bring over the next 4-5 years.
We have over 400 small molecules in our development pipeline. In the last four years, we've nearly trebled the number of biosimilars in partnership in development. Now with the position, we have 24 assets, as well as clearly the 8 assets that we've launched to date. More than 50% of the launch contribution going forward will come from biosimilars, driving the mix and driving our growth. In the medium, short to medium term, the next couple of years, we expect to launch at least 4 assets into the US and European markets. Again, you'll hear more about that from Pierre and Claire later today. We've also started investing in our future.
We recently announced a significant capital investment in Slovenia to build a state-of-an-art biologics manufacturing facility that centered around a current manufacturing capacity that we already have. We're also investing in our development capabilities by expanding our resources in Munich. We continue to leverage our strategic partnerships. We recently announced our partnership with Just - Evotec Biologics. This gives us a best-in-class technology-based platform to accelerate the speed of development and significantly reduce our costs. We really believe this will be a transformative deal and a transformative platform for Sandoz to expand our pipeline and to really drive best-in-class product. Again, Claire will take you through that a little bit later on today. We have partnerships with Polpharma Biologics, and again, we'll talk about the natalizumab launch, which we're excited to be bringing to the market later this year.
Clearly, we will continue to work with Novartis, both as a development partner and a supply partner in the short to medium term, as existing partnerships go forward. Ultimately, what's exciting about Sandoz, it's truly unique versus any of our competitors. We have technical development capability, medical regulatory, manufacturing technology capability, and significant commercial capability. We are the partner of choice for many of the leading industry suppliers and organizations. Let's now look to our future. Really, there are 6 key drivers that drive the fundamentals of this business. First and foremost, we operate in a highly attractive, growing market. We have leadership and scale in the geographies where it really counts. We have a diverse set of multiple growth drivers across broad portfolios and broad geographies.
As we step away from Novartis, we have clear plans to drive our margin expansion over the coming planning period. This will deliver strong cash flow, we can reinvest that back into the business and return capital back to our shareholders. All of this supported by an extremely compelling sustainability story. Let's talk about the market. Over the next nine years, we expect the market size in terms of the addressable market to nearly double, growing at about 8%. There's a few things that's driving that. Clearly, demographics, patients are getting older, governments are getting more challenged, there are significant LOEs coming up in the next few years, clearly, there's a technology shift to more complex and biologic platforms. At the same time, clearly, small molecules will continue to make a significant component.
We see strong growth drivers in terms of accessing that opportunity. Clearly, the biosimilar element is gonna be the fastest growing, with relatively lower levels of competitive intensity and significant growth driver opportunities. For me, in many ways, this is probably one of the most important slides because it explains why Sandoz is so unique. You generally look at our industry, the companies in the top right-hand corner tend to be the pure-play biologics companies, the Koreans or originators who thought to go into that space. What they don't have is the scale or presence in the market to leverage and drive value. Many then struggle or will have to form strategic partnerships in order to extract value.
It's also worth noting, in the top corner or the biologic space, five companies, including Sandoz, represent about 80% of the world market for biosimilars. It's already significantly consolidated, and we're a very strong player, currently ranked number two, but clearly with plans to regain our leadership. On the bottom left are the more traditional generic players, the small molecule players, the regional players, but they just don't have the capital infrastructure or technical capability to make the investment leap to deliver biosimilars. We have both. We have the cash generation and the scale that small molecules bring, but the long-term cash and margin expansion opportunities that biologics have.
There are strong synergies by having the two, both in terms of development, clinical, and regulatory, and Claire will explain that to you later, but also in terms of our commercial capabilities. Again, you'll hear from Keren, Rebecca, and Paco about how that really drives and supports our business. Having the two means that we have a stable cash flow. If you think about it, a small molecule takes about 2-5 years to develop, and normally $2.5 million-$3 million. A biologic, 10 years and $100 million-$200 million. Very different scales and very different kinds of return profiles. By having both, we have the cash from the small molecules and the margin expansion and growth driver from the biologics portfolio.
When you look about scale, clearly, Europe, we are very, very strong. A champion of a business, a leader in the majority of the markets in which we operate. We have a strong and dynamic international business and a U.S. business that now is stable, ranked number four, but positioned nicely to grow. Again, you'll hear from Keren about what those growth drivers do and how this business will develop over the coming years. When we talk about biosimilars, Sandoz defined this market. We were the first company to launch a biosimilar in Europe, Japan, and the U.S. 15 years ago. That biosimilar was human growth hormone, Omnitrope. I'm absolutely delighted to say today, this is the single largest human growth hormone product in the world.
We've you know, consistently taken share, consistently served our patients, consistently grown and developed our business. We're now ranked certainly in the top five, if not number one, in the majority of the leading markets in terms of biosimilars. We have the commercial presence, scale, and relationship. Bringing more assets to those markets drives significant value going forward. It's also worth reflecting that there's very few small molecule generics that you can have a 15-year life cycle, still be growing, and still delivering very attractive margins and serving patients. Incredibly proud of what the team have achieved. There are numerous drivers to our mid-single-digit top-line growth. We're guiding that our sales will grow mid-single digit between now and 2028. There's a number of drivers of that, excluding any incremental or transformational M&A.
We assume a very low level of M&A in terms of BD&L, which is about $100 million a year. Other than that, this is all exclusive of M&A. Clearly, sales execution, winning share, winning against the competition, maximizing the significant portfolio opportunities that we have by the products we bring to market, driving and improving our product mix, leveraging the strong strategic partners that we have as a commercial and development partner, and again, you're starting to see that emerge, and expanding the depth and breadth of our pipeline, investing in vertical integration where it adds the most technical and commercial benefits to the organization. I then said, additional M&A, clearly dependent on cash and finding the right opportunities that potentially support the strategic objectives of the business. On the margin side, clearly, as we step away from Novartis, there are a significant set of costs.
Again, Colin will take you through the bridge in terms of explaining how the investment to set up Sandoz to go forward. Our goal is to take our margin from high teens in 2023 to mid-20s by 2028, and really through a number of mixes. We think, estimate about 200 basis points from the volume, price mix, and the portfolios we intend to bring to the marketplace. Glenn will take you through a lot of the work that he's doing in terms of network design, our vertical integration, operational excellence, and building a world-class procurement organization that should add at least 350 basis points in terms of margin expansion. Lastly, stepping out of a large, complicated pharma organization, we see significant opportunities to separate, simplify and execute our operational model.
We've attributed about 150 basis points to that. This will expand our EBITDA from 18%-19% in 2023 to 24%-26% by 2028. As the margin expands, clearly, our cash flow, our free cash will expand. We expect to more than double that by 2028, sustained by core EBITDA margin expansion, increasing our EBITDA to cash conversion, and again, Colin will take you through that. We have a number of programs now already working in terms of driving our working capital optimization. We will have very clear allocation priorities for our capital. Number one, investing in our organic business, returning capital to shareholders, and then deployment into value-generating bolt-on M&A and BD&L in that order. This is actually very critical, maintaining optionality on our balance sheet.
We, at separation, are targeting to have an investment-grade credit profile. That's pretty unique in this industry, with estimate to have an EBITDA to core ratio about 2- 2.5x . Again, Colin will talk you through that, all driven with our prudent capital structure at spin-off, allowing it to invest in our business, drive our growth, and support our growth ambitions. This is our guidance on a page. As I said, sales guidance, maintaining mid-single-digit top-line growth in the midterm to 2028, driving our EBITDA margin expansion from high teens to mid-twenties by 2028. Supported by this will be a dividend policy, we'll pay a percentage of core net income in 2023, between 20% and 30%.
This will be on a full year basis, not just on the proportion of the year, but a full year. We expect to expand that up to between 30% and 40% of percentage core net income by 2028. All of this is supported by an incredibly strong sustainability story. Okay, one of the benefits of stepping out of a company like Novartis, and with the leadership of Gilbert and the incredible board that he's built, is a strong governance framework. Incredibly proud of our capabilities in that space. In terms of access, in a way, that is our business. Driving access, driving biologics, being the only remaining antibiotics manufacturer left in the Western world, is key to our whole reason for being.
As we step away from Novartis, we have very strong environmental credentials, and we'll give guidance on those commitments when we publish our annual report in early 2024. As an organization, we will continue to champion diversity, equity, and inclusion. Sandoz is extremely well-positioned, as I said, to deliver sustainable growth over the longer term. Clearly, attractive market fundamentals, our leadership and scale, significant number of growth drivers, a clear plan to deliver margin expansion, supporting strong cash flow, and our compelling sustainability story. Thank you very much, ladies and gentlemen. I'm happy to take your questions.
Sorry, I was just gonna say, for anybody who asks a question, please do state your name. Thank you.
Hi, Peter Welford, Jefferies. Can we, just going back to the geographic mix and the mix of the business, you talked a lot about biosimilars and how obviously that naturally is gonna grow. Can you just talk a bit about, from a geography point of view, how you think the split by geography could potentially evolve over the next, well, say, midterm, five years? Because obviously, the U.S. has been under a lot of pressure, but, I mean, do you see biosimilars as being catapulting, you know, the U.S. as a proportion of your business? And then just secondly, on the sort of manufacturing and the deals you outlined.
Apologies, this may not be the right time for this question, but you talk a lot about, obviously, the free cash flow going up two and a half times and free cash flow conversion, and that all makes sense. I guess, what about from the CapEx point of view? Presumably, you know, isn't this gonna be quite CapEx intensive over the next few years, given that portfolio of biosimilars you'd out licensed? How does that fit in still with the free cash flow aims?
Okay.
Thank you.
Thank you, Peter. Perhaps the second part first, Glenn and Colin will cover quite a lot of the detail in terms of CapEx, free cash flow, the investment in terms of stepping that up. Clearly, we'll continue to use Novartis over the midterm in terms of our supply, particularly around biologics. That's gonna be done on an arm's length basis, but still gives us a cost leadership platform to drive and support the business. The biologics, we don't break out the proportion of bio by geography, but clearly, with launching potentially four biosimilars in the short to midterm in the US, that's a significant sales and margin opportunity. I mean, clearly, adalimumab launches on the first of July. It's the single largest LOE in the history of the industry.
I know Keren will take you through quite a lot of the details in terms of that expansion. It's also worth noting, three of those four biologics will also launch in Europe over the coming few years. Again, there in Europe, we already have a strong leadership position. We have, you know, eight biologics already launched. Every single product we developed, filed, we've launched, and every single one, we're either number one or number two, and continuing to take share even many years after we actually launched those assets. I think Europe will continue to drive strong growth. Clearly, there's an acceleration expected in the U.S. Then international, it's one of the things I'm really proud of. What Paco has been able to do is launch biosimilars in markets that the originators couldn't even be bothered to do.
We're bringing biosimilars to unserved patients and growing. It's and a significant proportion of his business now, in terms of the acceleration, is gonna come from biologics as well. It's a nice mix. I guess the short answer is, it will be everywhere, but you're right, disproportionately in the U.S., given the opportunities that we see over the next few years.
Hi, Carson Wong with the Credit Suisse Pharma team. Just on the U.S. market, how do you view the future for biosimilar uptake in the U.S.? We have seen some rebate walls impacting the ability for some biosimilars to gain market share here. What impact do you expect from changes to the industry from the IRA?
Those are great questions.
Thank you.
Perhaps if I delay those in layman, because Keren will cover quite a lot of those later on today. I don't really wanna steal her thunder. I'll give her the opportunity to explain that, and then again, we can dig into that a little bit more in the Q&A, if that's all right.
Thank you. It's Mark Purcell from Morgan Stanley. Again, I don't know if it's the right time to ask the question, but could you more broadly talk about the sort of benefits and the challenges from the separation from Novartis? I'm sure you'll go into these topics in more detail, but just at a top level to begin with. The second question is on biosimilars. Do you believe it's becoming a more attractive or more challenging market? The question over there was on the U.S., but, you know, It's already a consolidated market. Do you see further consolidation, fewer players? You talked just about the geographical separation, which segregation, which I think is on slide 118, but it'll be really helpful to get a top-down view.
Sure. The separation, I mean, I guess unlike Alcon, Sandoz has never been a standalone business within Novartis. It's been a standalone commercial organization, development and supply organization broadly, a lot of the infrastructure, IT, tax, treasury, investor relations, all of those things were all managed by group. Clearly, that's one element over the last year, 18 months, with Colin and the rest of the team we've been building to have that stand-up capability. I think the biggest over the next 18 months, two years, a lot of the tech services will still be linked. There'll be a TS, or there is a TSA between Sandoz and Novartis to allow that system, the systems and processes. I see that as an opportunity. There's something like 1,500 shared software platforms between Novartis and Sandoz.
We don't need 1,500 shared software platforms. There's a significant opportunity to simplify and effectively shift those to being fit for purpose to run a generics company. I would say also, I mean, Novartis have been a good parent. You know, this is about creating two great companies. Clearly, Novartis is gonna continue on its own journey to become a world-class, innovative science company. What, you know, Novartis has done over many generations is invested in the business. I mean, they had the foresight to invest in biosimilars and give us the technical capabilities to do that. I think which is what happened now, is we've got the scale, we have the momentum in the business, we have the depth of the pipeline. I think it's now time for us to stand on our own two feet. We'll become two completely separate organizations.
In terms of bio, actually I'm pretty bullish, for a number of reasons. If you look at our bio business today, it's a few years since we launched a new asset in a market, in a region like Europe, yet it's still growing seven, eight, nine points, depending on the quarter. Something's going on that says: Well, why would a biologic that you've not launched for three years, still deliver seven, eight, nine points of cash growth? There's something else happening. When you launch a biosimilar, a lot of the time, those drugs are so expensive, they're third or fourth line treatment. A market like Poland, if you've got rheumatoid arthritis, it might take you five years to get best-in-class therapy.
What happens when biosimilars come, the price point clearly goes down. Margin is still very attractive. It means the patients get treated much earlier in the treatment cycle. You get a much more significant portfolio or a patient population expansion that drives growth. Looking forward, you know, it's still technically difficult. You know, a lot of the partners want to work with us because it's not an easy thing filing into the U.S. for a product like natalizumab. It's not easy having a site capable of doing that, and it's also complicated. You have a REMS program, we have, you know, testing and compliance programs and all sorts of things.
There's all sorts of opportunities and barriers, but that's an opportunity for us to create share. I think the journey for me has been, okay, how do we have the broadest and deepest portfolio? We started with about eight, three-four years ago, now we have 24. That journey needs to continue. Not all of it in-house, but clearly through partnerships and development. It gives us many opportunities to create value. The fact we're launching four biologics in the next, you know, few years is a significant growth driver, and clearly, we'll continue to look at expanding and doing that. I'm pretty bullish. I think not necessarily more consolidation, but I do see signals that some of the Korean players want to go in a slightly different direction in terms of innovator light or those kinds of directions.
Some of the other players that launch by a similar portfolio to complement their innovative portfolio, that cycle is coming to a close. You know, a number of the players, I don't see them necessarily expanding that. I guess it's consolidation, but not necessarily through acquisition or merger, more just through an divergent strategies.
That's very helpful. Just to the first question, I get the operational benefits of separation. In terms of strategic benefits, I guess there's no surprise that you've done more deals more recently, long-term strategic deals like the SPODS with Evotec -
Yes.
- as you approach separation. Can you help us understand the freedom from a capital allocation perspective, the separation provides, you know, the strategic flexibility for being a separate company? Maybe an overview there, or -
Yeah, sure.
- details later.
Well, I'll give you the top line, and then I'll let Colin give you through the details. I think, you know, we've tried to outline our capital priorities really clearly investing in, internally into the organic growth of the business. To the question around, you know, manufacturing and development, clearly key as we set up a standalone Sandoz. M&A is further down the list of priorities, clearly behind, you know, returning capital back to our shareholders. You know, the pipeline that we have, the plans that we have are here to deliver the growth. There's always a low level of BD in M&A, I was gonna say about $100 million a year of sales coming from that, but that's always been there.
We're not really targeting at this point any transformational M&A to either strengthen a geographical footprint or strengthen a pipeline or a portfolio. You know, what we have is currently in the plans. We'll continue to look at expanding it, but, you know. I think then the M&A phase is probably 18 months, two years further out as we sort of got the structuring set up, separated from all the systems from Novartis, driving up the free cash, and then start thinking about how we deploy it. If there's no more questions, I suggest we take a quick cup of coffee. Okay? Thank you so much.
Thank you very much. We're gonna try and keep the same timing because we have about 400 people online. If we have a little bit more time over Q&A, we'll still keep to the original timing. Thank you for bearing with us. Okay, now we're gonna move into the commercial part of our segment, really looking at our leadership and scale across our three main regions. We're gonna start with Region Europe. As I said, 50% of our sales coming from Region Europe, a real champion. We're the number one biosimilar player, and we have a phenomenal capitalization in terms of our portfolio and footprint. Region Europe is run by Rebecca. She's been President of Europe for the last three years.
She has over 16 years experience in the pharmaceutical industry, and 25 years overall working in Roche, MSD, and 16 years within Sandoz. We're then gonna go and spend some time looking at North America. Clearly, in many ways, probably the most challenging geography for the generics industry, but still the largest pharma market and a significant opportunity we see going forward. U.S. is led by Keren. Keren is a veteran of the industry, Comes from Teva, originally, was head of BD and M&A for them, head of the BD and M&A function for Novartis, and has done a phenomenal job stabilizing and really energizing the U.S. business. Now in a position where we're potentially launching four high-value assets in the coming time period.
Lastly, Region International, a diverse geography, but under Paco's leadership, who's had more than 35 years experience in the industry, has worked in many geographies, worked in both Novartis and in Sandoz. Really, he's been able to target significant market opportunities and significant parts of our portfolio and driving very attractive top-line growth, in a very executed and disciplined manner. Delighted to welcome the three of you. Rebecca, the stage is yours.
Thank you, Richard, for the introduction. Good morning, everyone. It's a great pleasure to be here with you today. As Richard said, my name is Rebecca Guntern. I'm 16 years with the company, and since four years, the President of Region Europe. The last four years have been an exciting journey, and together with Richard and my colleagues, we have been working hard on our ambition to become the world's most leading and most valued generic company. Today's presentation, of course, is a highlight and key opportunity for us to get you equally excited about our equity story and how we're gonna drive value in the future. In my role, of course, how do we do this in Region Europe?
Before I'm gonna take you how we have built the success in Europe, let me start to say that I feel truly proud to lead Sandoz in Europe. I do have an amazing team, and with over 1 billion packs sold, there is almost no other company who impacts the health of so many Europeans today more than ever. That's exactly why we feel proud to say that we do take care of Europe, and we're passionate about what we're doing every day. This is really what keeps me and my team going day by day to give our very best. Let's have a look at Europe at glance. Sandoz in Europe is a true commercial champion, with a clear market leadership in a growing and attractive market of the size of EUR 65 billion.
We do have a strong foundation and brand heritage, with commercial presence in over 40 markets. Critically, we're a top tier player in over 80% of the markets we're operating in. As you can imagine, this gives us huge scale, which is important in the off-patent industry, but also a strong and unique footprint. Together with our broad portfolio and leading go-to-market capabilities, this translates into a very powerful commercial platform, led by a highly committed and experienced leadership team. The business has delivered sustainable, profitable growth over the past couple of years, and is accounting for 50% of the total Sandoz turnover at $4.5 billion annually. We will build further in the future on this strong foundation and leadership position to continuously deliver growth in Europe. Let's have a look at the market.
The market in Europe is attractive, it's sizable, and it is growing. Important to know, the off-patent industry plays a very critical role, being the backbone of the European healthcare system. We account for 70% of all medicines dispensed, at 30% of the expenditure, and we have dramatically increased access for patients in Europe, namely in core therapeutic areas like cardiovascular and diabetes by over 100%, without increasing treatment costs over the same period. We expect, as you can see, the market to continuously grow, primarily driven by two factors. First, loss of exclusivities. We do see an LOE value of over EUR 100 billion in small molecules and biosimilars, with a higher shift to biosimilars. Now accounting for 15% of the market, we see this doubling over the next decade to 30% by 2031.
Sandoz in Europe is in a very strong position to capture on this market opportunity, based on our broad LOE coverage and strong pipeline. Second growth driver, volume growth. Fundamentally driven, as mentioned by Richard, by a growing and aging population, but equally, also cost containment measures, which will further accelerate and drive generic and biosimilar penetration. What is the role and the position of Sandoz in Europe? As you can see on the slide, we are the undisputable market leader with 11% share. We do have a strong and broad foundation, being the leading company in six out of the top 10 largest European markets, like, for example, in Germany, Spain, and Italy, just to name three of them. What is also important to know, we're the only top player with a very balanced portfolio between generics and biosimilars.
This is a key differentiator for us, which will enable us to capture on the future LOE value, important with the shift to biosimilars, but equally offers a very attractive value proposition for our customers. We have been outperforming this market over the last three years, which is reflected in the evolution index of 104. We doubled the gap to our second-largest competitor, moving from 2%-4%, driven by a strong and above-market performance in biosimilars, and also equally first-to-market launches. This brings me to biosimilars. Let me say that this is a true success story, biosimilars in Europe, and fundamentally, specifically for Sandoz in Europe. Sandoz was the first company to launch a biosimilars back in 2006 with Omnitrope.
Today, we are the leading biosimilar company, with eight commercialized product being ranked number one in five out of eight products. What is impressive is the fact that despite the very competitive landscape of anywhere between 4- 11 competitors per brand, we're still delivering year-over-year growth, and we have further expanded our market leadership position across the markets in Europe. Richard has already shared the example of Omnitrope, which is amazing to see after so many years in the market, and it's also true for Europe. We have further expanded our market leadership position in the last 12 months to 38% share. I would like to share another example, which is Hyrimoz. Launched back in 2018, we are now number one in 19 markets across Europe with Hyrimoz. We have doubled our volume share over the last three years, and we are delivering year-over-year growth.
Just in 2022, Hyrimoz grew by 23%. This is what is truly exciting when it comes to biosimilars, is the fact that there is a great opportunity to further expand the market by treating more patients and by treating them earlier. We do have the commercial capabilities to do so, including contracting and pricing excellence, but also pull-through in share of voice markets. This has exactly enabled us to expand our leadership position from 22%- 27% over the last three years. Based on what you can see here on this past performance and strong performance, I feel very confident that we will successfully launch and drive value out of our next four pipeline assets, targeting an LOE value of EUR 4 billion in Europe. This brings me to the financial profile of Sandoz in region Europe.
We are present in two business segments: generics and biosimilars. We have doubled the biosimilar business over the last five years, now accounting for approximately 30%. In 2022, the business grew by 6%. We saw strong volume growth, both in biosimilars with +70% and in generics, +7%, backed on a post-COVID recovery and strong market demand. We have been able to capitalize on this market growth, growing again above the market and further expanding our leadership position by 60 basis points. What is the success factors in Europe? Let me say that I see two main points. The first one is our strong commercial platform, and the second one, our leading go-to-market capabilities. This in combination, make us really a partner of choice in region Europe.
Now, looking at the building blocks of this commercial platform, I like to call it the hardware. I do see three main elements. The first one is geographical footprint. We do have a huge scale and strong presence with being in 40 markets, in 32 with our own legal entities. This gives us, of course, scale and a unique footprint. Second, with over 2,500 sales representatives, we have one of the largest field force in Europe, and this even beyond the off-patent sector. Last point is the portfolio. With over 900 products, we have one of the broadest portfolio among competitors, which is important for our customers to address those needs they have for the patients they treat.
These three elements fundamentally are core, and that's why we rank consistently among the leading companies across the major markets in Europe, as you can see here. Beyond the hardware, what is important, we know how to play and we know how to win across those market archetypes, which are tender, share of voice, and pharmacy substitution. This brings me to the software, our leading go-to-market capabilities. Talking about our leading go-to-market capabilities, this truly covers all elements which are important for successful commercial execution. We do have strong proof points and a track record when it comes to commercial execution. Starting the first step, market access. While Europe is one region, we do have 40 markets. 40 markets with different pricing and reimbursement policies.
Absolutely important to understand how do you enter a market to get price and reimbursement, and of course, that you can sell it at the end. We know how to drive market access. We have been front runners in driving policies and shaping the market environment to ensure sustainability of the industry. We have been leading when it comes to define criteria for tenders beyond price, and fundamentally, also introducing gain-sharing models in biosimilars, namely in Spain and in France. Launching. We know how to launch a product, being first to market in 70% of the products we're launching. In combination with our broad LOE coverage, this is truly the core skill set of an off-patent company. Last but not least, selling. We know how to sell, and we know how to sell across market archetypes.
In tender, we have a high win rate, and we're winning many tenders, not because of price, but at criteria which are product features, quality, and supply. In share of voice, we're leading in face-to-face share of voice, which is super important to really drive prescriptions at physician level. When it comes to pharmacy substitution, where the pharmacist can switch an originator to a generic product, we do have a very broad and strong access to pharmacy networks, which is enabling us to drive broad distribution and a fast uptake, specifically for launch products. Bringing it together, both the commercial platform and on top, our leading go-to-market capabilities, are really differentiating us from our local and global competitors.
It is very difficult to replicate them in the way Sandoz has built them over decades, being a very trusted brand for payers, for customers, and for patients. Looking at the future, I have talked you through now how we have built a success in region Europe, and I'm very confident that we're well positioned to continuously deliver sustainable growth in Europe. As presented by Richard and as outlined here, in essence, it is a continuation of our growth strategy. We're gonna do more of what we have done successfully in the past, namely relentless focus on commercial execution. We want to leverage our unique footprint and our scale, maximizing our pipeline value. We do have a very attractive pipeline with $20 billion of LOE in the next five years to come, and we can leverage our first-to-market capabilities.
We're gonna see continuously a product mix shift to higher margin biosimilars. We will build strong strategic partnership, leveraging our commercial platform. On top of that, we will continuously invest into the breadth and depth of our pipeline. To conclude, Sandoz in Europe is a true commercial champion. We're operating in a very attractive, sizable market, with market proximity and the reach, which differentiates us from our competitor. We do have an outstanding track record in commercial execution and an ability to win across market archetypes, something my experience tells me is absolutely key to win in Europe. With those core skill set and strengths, and I would say with a highly committed and capable team and a very clear plan in place, I'm very confident that we will continue the success in Europe, and we will continue to deliver growth in the future. Thank you.
Let me introduce Keren, my colleague, who is the President of North America.
Good morning, everyone. Thanks, Rebecca. Thanks, Richard, for the introduction. Great to be here. I joined Sandoz two and a half years ago, and it was a special opportunity to join a company where my personal why and my professional why are coming so well together. My personal why is all about people and making a difference and impact in people life. At Sandoz, we have an amazing opportunity to make a huge difference in patients' lives every day. I'm privileged and inspired to lead this organization every day. I was reflecting when I was preparing to this session on how I'm gonna share the North America journey that we've been through. I was thinking about our story, and our story, think about, as a book, has three chapters.
Every chapter in our book has one key message that I want you to take away from this session. The first chapter is about we stabilize the business. The second chapter, we have the right team and strategies in place. The third chapter, we are ready for our exciting upcoming launches, and we are entering our growth phase. Before I go into my book, let me give you a bit of an overview of our market. The North America market is a $75 billion market, which includes two countries, U.S. and Canada. As you can imagine, given the size and dynamic of the U.S. market, most of my presentation, I'll focus on the U.S. The market is expected to grow 10% over the next 10 years, and as you can see, tremendous growth in biosimilars. 24% of the growth expected in biosimilar.
Now, this is a unique opportunity in the U.S. because the access for biosimilar is not where we want it to be, and this is an opportunity to serve patients early and give them the opportunity to get into the biologic drugs that without introducing biosimilars, they will not get access to. If you look at the small molecule market, it's also growing, with 6% CAGR, driven by LOE opportunities. The market is already well genericized in the U.S., as you are well aware. 90% of the volume in the U.S. is filled by generics. This 90% account only for 3% of the overall U.S. healthcare expenditure. It's so important to continue and serve patients. As you heard from Richard, we're uniquely positioned to be this pure bio.
Pure play, sorry, bio generic company that will be there to serve patients in both generics and biosimilars. We have a leading position in both U.S. and Canada. Let me start with Canada. We have a very strong business in Canada. We have experienced and committed team that continue to grow share in the market for the last seven years. We are committed to the patients in Canada. We'll continue to do everything we can. As you can see, we were the only company that grew in 2022 and will continue to consistently grow and close the gap to be the number one in Canada. As I mentioned, most of my presentation would be on the U.S. today. This is where chapter one begins. We stabilize the business. This is our evidence.
We are one of two companies that were able to grow in the market in 2022. We had strong sales of $2.1 billion, 80% coming from generics, 20% from biosimilars, and we declined 2% versus previous year. As you remember, this is a business that came a long way. This business suffered from lack of portfolio investment due to our decision to divest in 2018, our derm and oral solid portfolio. We decided to divest this portfolio, and the transaction didn't go through. The FTC didn't approve the transaction. We reintegrated the business in 2020, but as you can imagine, it takes time to rebuild your portfolio.
I'm very proud, and I'll tell you, of course, in more detail of all the work that we did with Claire and her team to rebuilding our portfolio in both generics and complex generics. We didn't want to wait for the portfolio. We wanted to make sure we stabilizing the business. In order to do it, that's where my chapter two begins. We talked about having the right team and the right strategy. Let's start with the team. You cannot turn around a business without having the right team in place. We have a very skilled, committed team that is working every day in the market to win share. As I said, and as you saw in my previous slide, we were able to do it, and I'm very proud.
The culture that we have in our company and the people that we have is the one thing I'm proud the most. There are many things that go into turn around a business, I was thinking what will be the best way to share them, I focused on three elements. The first one is commercial execution and focus. We have a very broad portfolio, in order to increase share, we thought what we can do. As I said, pipeline would come later, right? We knew that it takes time to build pipeline. What we decided to do, we looked at the entire portfolio, we decided to act on execute when we feel that we have a competitive advantage. It could be from a price, from a cost, or from a supply perspective.
We worked hard to focus on this portfolio where we can win, and as I mentioned, we had a lot of success, and we were able to grow our share. The second thing is focus on our launch excellence, because as you know, we have significant number of exciting launches, and we wanted to make sure that we are making it perfect. We have a very strong experience and skilled launch team that work very hard every day and well-equipped to bring product to each one of the channel, if it's the buyer, retail, or hospital market. The second thing that we did is looking at our customers. When I joined the U.S., there was this perception that the only thing that matters is price. I can tell you it's not correct. Again, having this relationship with your customer, building this trust, it's taking time.
I'm very proud, and as I said, the only way you can do it is having the right team. You build trust with people, not between companies, and that's what the team did so well. We had the right conversation, not always the pleasant conversation. Also, being able to have the tough conversation, but doing it in a very respectful and transparent way made a huge difference for us. Now, beyond that, we said price matters, but, you know, Rebecca talked about it in her presentation. It's these three elements that really makes a difference in our market. It's price, it's quality, and it's supply. Very proud of our quality heritage, and I think there is no doubt that the Sandoz brand give a lot of quality heritage. Supply, that's where I'm proud the most.
We were the first company to introduce biosimilars to the U.S.. We introduced biosimilars in 2015, I'm very proud that we had 100% supply reliability into this market. That makes a huge difference for patient, because what access mean at the end of the day is that the patient can get a product when they need them, at the right time and at the right cost. Last but not least, and this coming back to the pipeline, this is the lifeblood of our industry. The only way to offset the price erosion in our industry, specifically in the U.S., it's to launch product. We had focused the U.S. portfolio in a very attractive pipeline from both small molecule and biosimilars. We worked very hard with clearing our team.
We double our ANDA submission in the U.S.. We focus on opportunities when we can be first to the market. 70% of our portfolio is the opportunities to be first. It's either exclusive share to file, first to file or first to market. Again, this pipeline is coming very soon, and the exciting part of this pipeline that I want to take time and share with you is where actually chapter three begins. It's our launches, our upcoming launches. We have four upcoming launches, which account for $30 billion of loss of exclusivity. We are very excited for what we can do for patients in the U.S.. As you know, in the U.S., there are two channel to sell your biosimilars, the medical benefit and the pharmacy benefit.
Our first launch, Adalimumab, which we are very excited and it's around the corner, it's into the pharmacy benefit space. This is a unique opportunity for us as an industry to write a chapter in, you know, in the books of history. This is $18 billion loss of exclusivity, the largest ever loss of exclusivity in the U.S. . We are just coming off our launch meeting. I can tell you the excitement and the enthusiasm to be able to bring patients this drug, it's just inspiring. If I could show you the videos and the energy, it's just hard to describe. As you are well aware, this market is gonna be very competitive in the US, but we feel we're uniquely positioned to be leaders and win in this market, mainly because of three reasons.
Our formulation, our high concentration, citrus-free formulation, which we believe is the best formulation for patients. Our experience and leadership outside the U.S., and you heard from Rebecca how well we are doing with Hyrimoz in Europe. We are number one in Europe. We are number one in Canada. We have 120 million days of patient experience in transitioning patients from the brand product to the biosimilars. That's critical when you enter a market. Patients feel very comfortable, and physician, that they know that the company that they are working with has this experience and capabilities, not just to transition the patient, but also to support them throughout the disease journey. We know those are chronic patients that need this support, not just a day or two in their life, every day. Last but not least, our supply.
As I mentioned, the most critical element in this launch is to be able to supply the market. We feel very confident that we have the supply that we need to support the market. As I mentioned, with our 100% supply reliability so far, we not just have the confidence, we know that we did it in the past and will continue to do that. The three other biosimilars, they are going into the medical benefit space. It's a very different channel in the U.S., where we have tremendous experience. Our biosimilar portfolio, our current portfolio, is in the medical benefit space. We were the first company to launch in 2015 after the BPCIA was introduced. We launched our own Zarxio. We still have our leadership position in the market.
Three launches, all of them will come to the market upon FDA approval and IP clearance. As you are well aware, the IP landscape in the U.S. is complex. Litigation is part of the business. In order to bring biosimilars to the U.S., you need to litigate, and we are in this process, as you can see in the footnote for all of them. In each one of them, I want to leave you with the key message. Let me start with natalizumab. Natalizumab is the biosimilar to the reference product, TYSABRI. We have a unique opportunity here. We are the first to get into the market and potentially the only one, we are not aware of other competitors that are expected to come in the near term.
Secondly, TYSABRI has a very complex profile from a safety perspective, and we have the experience and the right support system for patients to make sure that we continue to serve patients safely. The next one is denosumab. Now, we expect to launch into both the oncology and the osteoporosis phase, and here we're gonna leverage our experience and skills. As I mentioned, XGEVA is into the oncology space, where we already have our portfolio, and with Prolia, we believe that we'll have a lot of synergies with our Humira, with our adalimumab launch. Last but not least, aflibercept. We will launch both the prefilled syringe and the vial, and we have a unique opportunity here to continue to put patients in the center.
You can imagine, when you inject a medicine into your eye, you want to work with a company that can be there and you trust. We're very proud to be this company. As you can see, many launches in many therapeutic areas, which will help us to serve patients and continue this journey, which I'm very proud of. Coming to the cliff notes of my book, we'll continue to execute on our sales. We'll maximize our upcoming launch, which have a significant opportunity to serve patients and introduce significant opportunity from a dollar perspective, $30 billion LOE in the biologic space and $53 billion in small molecule. We will continue to improve our product mix, thanks to those launches, and leverage our strategic partnerships to ensure we get products either organically or from externally.
We need to remember our patient, they don't care where the product come, as long as they get it at the right time and at the right cost. Last but not least, our lifeblood of our industry. We'll continue to invest in our pipeline, both in small molecule and bio. Just to conclude, remember the 3 key takeaways that I want you to take from this session. We stabilized the business. We have the right team and strategies in place, and we are ready for our launches and entering our growth phase. I can't wait to update you on our next chapter. Thank you. With this, I will hand over to my colleague and friend, Paco.
Hi, good morning, everyone. We have been, during the last few minutes, listening, our business in Europe from Rebecca, very strong commercial footprint, and also we heard from Keren, how she did turn around, together with her team, the business in North America. That has been an outstanding story. What I'm going to do in the next 10 minutes is share with you what we have been doing in Sandoz International Region, that is covering the rest of the world beyond Europe and North America. My name is Francisco Ballester. I'm known as Paco, that's a nickname, and I have been in the industry for the last 35 years, 32 in Novartis, the first part in innovation, and the last 11 years as part of Sandoz International Region. This is my responsibility to share with you the past, the present, and the future of Sandoz International.
Sandoz International is covering geographies that is up to $68 billion business, and this is a growing business, very attractive, that we are running in the global scale. We have been doing, in the last few years, a lot of focus and dedication, as Richard mentioned before. We have been reporting $2.5 billion revenues in 2022, with a 7% growth not only in 2022 but also during the last four years. The growth what we delivered in 2022 and the previous years was based on a very clear strategy. We made some decisions five years ago when we created Sandoz International Region. Sandoz International Region was a newly created region among several geographies in the world, which were clusters or sub-regions at that time. When we put them all together, we make three decisions.
Number one, we decided to focus on people and culture, working on a winning culture in order to make a difference. Second, we decided to operate in a very lean approach, working with a generic mindset. The third one, we decided on five pillars, five pillars of strategy that I will share with you in the next two minutes. First of all, we decided on specific geographies we wanted to play and geographies that we wanted to exit, We went from 120 countries to 26 focus countries in this period of time.
The other one, we decided not only to operate in the specific geographies, but also to decide which were the segments where we wanted to play, and the segments we wanted to play within the specific countries or geographies, because we knew that we didn't want to play everywhere in every country, and we wanted to decide where to invest and where to make the difference. The other one is that we also streamlined our portfolio. We decided to select the specific products where we were competitive, and as a consequence, we were able to make a difference versus our competition in the local specific markets. I will also mention how we did it, and how we streamlined our portfolio in the next few slides.
The next one is we also focus on our launches, making sure we were doing more launches, more frequent, more successful, and expanding our first-to-market opportunity. We moved from 10% first-to-market launches to 25% in 2022. We're looking forward to expand up to 50% in the next two years. The very last one, we did both, a combination of leveraging our global portfolio and bringing that to the geographies that we have selected, together with BD&L opportunities. That means signing contract with third parties in order to do business development and license contracts with third parties that are, most of them, multi-country, in order to do the simplify approach and do not make a lot of deals across the world.
These multi-driver that I mentioned before to you are the ones making the difference in Sandoz International, delivering this consistent 7% growth or above in the last few years. The market is attractive, that's not a question. Market is attractive because it's $68 billion, as I mentioned before, this $68 billion is equal to North America or Europe, it's big, sizable, and growing 5%. This is based on the economies that we are operating. it's based on the population, it's based on aging population, and beyond that, there's an expansion on the healthcare coverage in the different geographies of the world. We have, obviously, as I mentioned before to you, selected the specific pockets of faster growth within the geographies where we are operating. We don't play everywhere, because where you invest matters.
We decided where to invest, where not to invest in the specific geographies, and I will cover later. One clear example is biosimilars. In the case of biosimilars, we'll be growing in the next 10 years, 4- 5x faster than the standard small molecules, and that is obviously a focus and a target audience for us. The segments. I mentioned to you that we are operating in the specific geographies, but beyond that, we select the segments where we can be competitive, and we can make a difference. We select these specific segments. One of them is substitution, pharmacy, INN. The other one is share of voice. Share of voice that could be either in a specialty or general practitioners, or we go to tenders.
Tenders that could be, we choose multi-country, or we choose tenders that are multi-years, or we choose tenders that are either national or regional, and we make that decision where we can be attractive and competitive. We can also choose either hospitals or OTC. These are also options that we eventually decide in the specific geographies. These decisions are based on patient needs, market size, market growth, and the value creation, how we can grow over the like, next few years, not only considering what it is today, but what we can do in the future. There's another point here about the number of countries that we serve through third-party distribution. I will cover this in the next slide. How we need to expand our business in growing 7% on the last four years.
We did it with a lot of focus on the attractive markets I mentioned. We also implemented an effective, successful approach with satellite countries. These are the ones that we serve through third-party distributors. In the satellite countries, what we serve through third-party distributors, we do it with a similar portfolio that we do in the mother country, the country is supporting the satellite. As a consequence of that, we simplify portfolio. We have similar regulatory framework, similar portfolio and SKUs, as a consequence, we leverage our volume, simplifying the portfolio and improving our outcome in the supply that we do in the geographies. Harmonizing this portfolio, as a consequence, it is an enabler in order to get a better COGS, as a consequence, serve with higher margin in the future.
The other reference I want to make, it is the first to market. I mentioned that we have expanded from 10%- 25% in the last three years. This number, I want to highlight, that is creating significantly more value. We create value 3- 4x higher in top line, but also in margin, every time we do a first-to-market launch versus when we get late to the market. Beyond these comments, we also did a couple of inorganic acquisitions in the last three years, and I will mention them and the details in the last slide before we close. Two specific examples of this model, where we target the country, and we target the segments, and we make decisions in order to be consistently growing over time during the next few years. One is Australia.
These two markets are fast growing, 50% per year in the last three years, but they are not the fastest growing, but they are sizable, so as a consequence, they are representative of the decisions and the outcomes we made in the last few years. In the case of Australia, we decided to go from a local approach to a global approach. We maximized launches, we went to the global portfolio, and we selected the ones that we were able to launch in Australia. The last three years, we launched three times more products in Australia than what we did in the previous 10 years. We massively expand our launches in Australia.
Second one, consequence of our new portfolio and launches that I mentioned, then we went to more key accounts, and we were able to access more pharmacies and change in the market, and that was a significant growth versus what we did in the previous years. The last one is biosimilars. The launches in hospitals and biosimilar was significantly more efficient, because we understood that the growth in the future was going to be biosimilars, so we over-invested in that area in order to be successful, as we did in the last three years. Second example, Brazil. Brazil was 100% focused on the pharmacy business a few years ago, We shift from that one to a model where we now have our three pillars. Number one, we remain with the pharmacy, but we deliver lower scale.
We went to the branded generics, specifically, what we did in antibiotics. Beyond that, we have been investing in biosimilars. The case of biosimilars in Brazil is through a third-party distribution with the government and consortium. We have a 10 years deal with the government. This supply agreement with the government creates reliability in Brazil. As a consequence, it is more predictable than other cases that we go for tenders year-over-year in different geographies. All in all, it is decisions we made in the different geographies. This is just an example illustrative of what we have been doing over the last few years. Two examples of acquisitions. One is the business that we acquired in Japan, the Aspen business.
We integrated in the last couple of years, and this business has been successful. Beyond the success, this was a strategic asset because it gave us access to the channel in the hospital, where we didn't have before. According to the complex products that are coming to our portfolio, we have been leveraging that opportunity in order to be able to access the hospital business in Japan in the next few years. The second example is the antibiotics and cephalosporin. This is branded, which is according to our strategy international. Beyond that, we have the opportunity to create synergies with our commercial footprint around the world, because we are leaders in antibiotics in many countries. Beyond that, obviously, we will integrate the antibiotics in our manufacturing setup across the next few years.
In summary, I'm very confident that we will continue to be growing in Sandoz and in Sandoz International region in the next few years. Why? We have the right pillars. We have the right team, the right culture. We have the right countries. We have selected the right segments within the countries, and beyond one, we are doing more launches, more frequent and first to market, creating significantly more value. The mix. We are expanding to complex products, and we are expanding also to more launches in biosimilars, and as a consequence, the margin expansion will be helping us to deliver better outcome for the shareholders. The last two, we are maximizing the opportunities to partner with third parties. We are the partner of choice.
We're a multinational present in the right countries across the world, beyond Europe and North America. Last one is portfolio. We are doing more and better every time in our portfolio. You will hear that from Claire and Pierre in the next few minutes. Because we are doing more and better, maximizing and launching first to market across the world is giving us the opportunity to create more value and more access for patients in the world. I will hand over to Richard for Q&A. Thank you, Richard.
Take a seat. Thank you.
Thank you.
Thank you so much. Thank you, Rebecca, Keren, and Paco. I'll now happily take your questions. I'll start with one and then other people...
I guess, I don't know how much you, any of you are going to be able to say necessarily on this, but particularly Keren, but I guess the obvious one is we're obviously seeing with adalimumab biosimilars in the U.S., a number of different strategies that have been employed or will be employed.
Not expecting you to say what you're going to do on July 1st, but can you just talk a little bit about, I guess, your interpretation and how we should think about this, and how, you know, they could play out in the U.S., and how you're thinking about the adalimumab market evolving for you over the course of, I guess, this year and next? Maybe on a similar vein in Europe, I guess, could you just talk a bit about how the pricing and the dynamics have changed since they were originally launched in Europe? I know obviously, there's been some very aggressive tenders initially. You know, I guess, what were some of the initial pricing?
You know, has it eased somewhat, or is it just, you know, continuing, if anything, to get even more aggressive, over time? If you talk a little bit about, you know, how you see that evolving in the future.
Keren, do you want to go first?
Yes, sure. Thanks for the question. Look, as I mentioned, there are two channels in the U.S., right? In the pharmacy benefit channel is where we have less experience as an industry. I think it's not a question for me of the kind of if it's gonna happen, it's more the when. You know, we see a lot of different strategies, as you mentioned, which is expected when you have such a competitive market. We do believe that it will take time to market to form. We don't believe it will happen this year. I think we also, you know, that Humira will continue to be in a preferred formulary, and the biosimilars that will be introduced by the payers will be in a parity position.
I don't think that there is a real opportunities for biosimilars, again, as an industry, when you are in a parity position to the innovators, but I 100% confident that, you know, the payers will displace Humira. When it will happen? You know, We don't know. We assume it will be in the mid to short term. What I can tell you is that when it will happen, we are very confident that we have the right strategy and the right pricing to be able to win in this market. As I mentioned in my presentation, you know, we have a lot of discussions with payers. There's three things that makes a difference for them is the formulation, is the, our experience and ability to transition patients, and then, of course, our supply reliability.
Rebecca?
Yes. Let me quickly frame your question on pricing in Europe. Fundamentally, I think the price impact we're seeing is dependent on the competitive landscape. This is one element, and the second element is the archetype.
The roughly 50% of our business is tender, the rest is share of voice, and in many cases, like Germany, we have still a big part, which is share of voice. What we are seeing is pricing depends, of course, on the maturity of the portfolio, and we do see stabilization. I would say high single-digit, in average, is the price erosion we're seeing in biosimilars, and it has been stable. If I look at the last year and compare it now to Q1, it's stabilizing. This has, of course, to do that we work very intensively with governments and also with the authorities and procurement partners, to go and to define criteria's beyond price.
If you take France, for example, over 50% of the tender is already beyond price criteria, like product features, supply, quality, which is a big part if you think it through. We see more and more countries going into multi-slot tenders and really shaping these tenders to make it more sustainable because they understand that they need to change the thinking. It's not just price. You need to have the product to treat patients and have the impact on the system.
Also, actually, you're continuing to get the volume expansion, that you don't get a small molecule, so you still see strong underlying growth for biologics years after they're launched in a way that you wouldn't see the small molecule.
Thank you. It's Mark Purcell from Morgan Stanley. Three topics, if that's okay. The first one's on BioBetters. Could you so help us understand the importance of this in your different regions? I guess in the U.S., the concern investors have is if the branded innovator squeezes down on price, but you have differentiation in terms of your product offering, how important that is. And I guess in Europe, the best example I can think of is Omnitrope, where it was a BioBetter from the beginning and took share from the innovators. The importance of BioBetters in your strategy, that would be great. The second question was on IP success. In one of your slides, you talked about success with pirfenidone.
Is this marking or representing a shift in the balance of power when it comes to IP, or is this just a product-specific situation? I guess there was a topic and a question earlier around IRA. I'm just wondering if IRA potentially changes the dynamics when it comes to settlement agreements, where obviously you were on the wrong side of a situation with Enbrel, which locked you out of the market until 2028, which comes in the scope of, I guess, the direct price negotiations we're about to face based on IRA in certain markets or certain products rather. The last one is interchangeability, just following on from Peter's question. How important is interchangeability in your three separate regions?
Okay, perhaps we'll break the questions down. I'm going to ask Pierre to answer your first question, because I think he can then look at that as a landscape. Clearly, you know, we have strong lifecycle management, and I don't recognize it in terms of a BioBetter. We're not trying to be innovator light or clinically differentiate. I think where we can innovate and change is maybe the formulation, presentation, or delivery mechanism. So I'll ask Pierre to pick on that. I think, IRA, clearly, I think, you know, Keren's extremely well-positioned. I think the last bit on the patent landscape. Look, you know, I think it's one of the things that's clear, we have a standalone Sandoz. You know, part of the reason for being of a generics company is to challenge and push that.
As we become an independent company, clearly, that will be part, continue to be part of our strategy. Pirfenidone, I think, is a really great example. You know, a lot of our competitors chose either to settle or not to challenge. We challenged, we won, we launched, and I think, you know, we will continue to do that. I think the team that Ingrid's built is extremely capable, and clearly, you know, we will continue to challenge patents in the U.S. and other territories. Do I see a sea change? I don't necessarily on the patent landscape. The U.S. is always, it's always been a feature of that. Interchangeability, I'll perhaps speak at a macro level, and then again, we'll close then with Keren on the U.S.. I mean, Europe is already, biologics are interchangeable anyway. It's a, it's a non-debate.
That, you know, so, you know, we don't really see that as a key differentiator. The fact that you get it, you're, you know, you're approved, and as an MA, the assumption is it's interchangeable, and I think the acceptance in Europe, broadly for most markets, is there. I think the U.S. then we'll pick up separately, last, but perhaps, Pierre, do you want to start off with the differentiation?
Sure. Thank you, Richard. Our strategy clearly is to follow the biosimilar route for our product selection and for development. I'll explain why we're confident in that and what that means. We're confident in that because that means that we can follow the biosimilar development pathway, which is efficient, well-defined, well-characterized. Within that pathway, there's a lot that you can do to ensure that you've got meaningful differentiation for your product where it matters. That can be the device, that can be the shelf life, that can be out of fridge stability data, that can be needle gauge and other features and benefits that come with the product.
In my later presentation, I'll give you very tangible examples of where we've done that, and really, to Rebecca's point about tenders, be able to win tender criteria based on those advantages. Now, on the BioBetter aspect, here, this is from a strategy perspective, not in scope, because ultimately, it follows a different regulatory pathway, usually resulting in a product that is so meaningfully different that you have to follow an innovator pathway, invest in a large clinical trial, which typically would be hundreds of millions of dollars. That is not in our strategy. We feel very confident with our pipeline that we can deliver meaningful success with a biosimilar-defined strategy.
IRA?
Yes. On the IRA, you know, I will start and say that it's very different, you know, the view for the generic and the biosimilar industry versus the innovative medicine, you know, industry, and there are pros and cons in the IRA. Where we are concerned is the unintended consequences and how it would look at the incentives to continue to innovate and bring, you know, and for us, biosimilars, as you heard from Richard, it's cost a lot of money, and it takes time, so you need to make sure that you have the market by the time you get there. Again, as I said, there are also pros, we're still assessing. I think for me, the guidance of CMS, the final guidance, and how we implement the IRA, that's what will make a difference.
There are still a lot of open questions, and we'll continue to work with them very closely. We need to remember that at the end, this is just in the government setting, right? It's not the commercial business. It's just on the Part B and Part D. Of course, we'll continue to work with them. The negotiation is the part that we are concerned the most, as I said, the unintended consequences, and it's coming back to my presentation. We do a very good job as an industry to reduce pricing in the market. We believe that the best way to reduce price is competition, and our industry is doing a great job, 90% of the volume and 3% of the value. That's on the IRA.
Can you pick on interchangeability?
Yes, on the interchangeability, what I want to pick specifically for the U.S., you know, we need to remember, interchangeability is not a better product, right? It's not from a quality and not from a, you know, safety perspective. It's just a regulatory designation. The importance in the US, I would say, time will tell. It's very different feedback from different stakeholders. We believe that you could win and be very successful in the market with the attributes that I mentioned in my presentation. We don't believe that interchangeability is a key attribute, but we definitely recognize that it's one of the attributes out there, and it does allow, you know, pharmacies to switch without calling the physician. It does give a operational benefit. We believe that we are equipped to win in the market without it.
Anything you want to add, Rebecca?
I'm just for Europe, it's clear, right? Because EMA in April 22nd gave out a statement that any product which is approved by EMA is interchangeable with the originator and with other biosimilars. In Europe, it's basically what we see in practice is also now confirmed by EMA with an official statement.
Thank you.
You look surprised.
I'm not nervous.
I have three questions from Balaji Prasad from Barclays, who wasn't able to join us in person. The first one for Rebecca: What disadvantages, if any, would Sandoz face in Europe by not being part of Novartis? Two for Keren: In North America, how is Sandoz geared to differentiate itself from peers and offset the pricing dynamics that most of its peers face? The second for Keren is, what are your thoughts about the direction of EBITDA from North America in the small molecule generic segment? Will it face a similar upward trajectory as the rest of the business?
Sorry, can you repeat the last sentence?
Will it face a similar upward trajectory as the rest of the business?
Rebecca?
It isn't. We have been, I think, looking at the disadvantages, have been actually operating pretty separately already in the past from a commercial point of view, right? As I mean, different when you think about supply or development, but commercially, we have been independent almost. We see this now, also, there's almost no detanglement. I don't see actually, a disadvantage, from a commercial point of view.
Yes, thanks. So for the first question, you know, the best way to offset the price erosion is launches, as I mentioned in my presentation. We have a very strong portfolio, both on the small molecule and the biosimilar side, so that the way that we will offset and differentiate ourselves from the competition is by execution and by launching product. That's the, this commercial engine that we have and will continue to launch products. For the second question on the EBITDA and the small molecule, again, we will continue to improve because we've produced more complex product. Again, Claire will cover it in her presentation. In the small molecule, we have great portfolio, both from, you know, oral solids, but also from a much more complex product that will help us to continue and grow our EBITDA.
We need to remember that we have this unique scale. We have a large portfolio and infrastructure in small molecule. The additional bringing more portfolios, just using the scale and infrastructure that you already have. From a margin perspective, it's allow you to really grow once you introduce more products into the market.
Hi, this is Katarina from JP Morgan. Just two quick questions. One on to Tysabri, anything you can say on the litigation front in terms of dates for any court trials and what gives you confidence maybe in that patent that it'll go your way? Then the second question is on the oral solid business, I think in the presentation you mentioned you tried selling that business at some point. As you know, sitting where you are today, like, do you see that as a core piece of Sandoz, or is that potentially something you can, again, explore, kind of, you know, either divesting or doing something else with?
Perhaps I'll comment on the first part, and then I'll let Keren just talk about, you know, the thoughts about the synergies between the businesses. I mean, clearly, we're, you know, we're going through a patent dance. It's normal part of the process. We wouldn't normally disclose any specific details around that other than, you know, clearly, we're confident we have a great product, and we look forward to clearing the landscape and hopefully bringing that to the market in the latter part of this year. I guess watch this space, and we'll see what happens. The cons, I guess the Aurobindo thing was an interesting one.
It clearly shows that some of the challenges trying to divest in this environment, and I don't think that environment's got any easier, actually, with the current FTC. I think actually, in the end, what we've ended up with now is an intimacy and a scale in the U.S., particularly around how we supply our pipeline, the relationships with customers, and our credibility, that having that broad portfolio, clearly, it took some time to wash it out, stabilize it. I think now you're also starting to see an environmental change in the U.S.. Clearly, supply is in the news all the time, and clearly, there's a lot at the moment. Having a broad portfolio and a relationship, actually, I think, gives us more strategic advantages. I think Keren is clearly the expert.
Yeah. Thank you. We definitely have a lot of synergies in the business. you know, it goes from IP capabilities, which again, definitely, you know, goes in both small molecule and biosimilars into market access, into supporting patients. You know, we talked about all our ability to support our patients with the biosimilars launches, but we already have those hubs. We have a lot of complex generics product that we already bring those support to patients, and of course, the existing bio portfolio. Other than that, I would say we will continue to leverage the expertise. Some of the expertise, like contracting, we're doing together. Some of our customers are the same, the payers are the same.
There are a lot of synergies when you look at it from a business perspective, and we are very proud the way we operate now in three channel, when we have bio, retail, and hospital, but our back end is really consolidate because we do have a lot of synergies. We can use the teams to work with each one of the channels.
Thank you.
Hi, Carson. Hi, Carson Wong from Credit Suisse. Just one for Rebecca. You presented that the European generic penetration rates are significantly lower than. There's still some, quite some significant revenues from branded off-patent products. Do you envision that the European market can ever change to move towards the U.S. in terms of generic utilization? One for Keren. US generic pricing has gone through a number of cycles. What do you see as a sustainable pricing trend for both biosimilars and small molecules? Thank you.
Rebecca?
Yeah. It was not so easy to understand, but I understand the question was the generic penetration in Europe and whether we see it as an acceleration in the future, correct? Yes.
Would it end up looking like the US?
Like the U.S. you know, Europe, and I think this is also the beauty in Europe, we have 40 different markets. Which makes it attractive in terms of the mix of archetypes you have, and most probably, the risk profile, which is a bit lower because you have really these different market policies and frameworks. Fundamentally, we do see a difference in generic penetration in Europe. Of course, the tender markets, by definition, you would see higher penetration, and if you go to share a voice, it takes a bit more time to pick up on the generic penetration. We see an acceleration overall, for the reasons I presented, that, of course, we see cost-containment pressure coming in, which will drive generic and biosimilar penetration, and you're gonna have an aging population.
By definition, you're gonna see volume growth, which will go into the generic penetration. Will we become U.S.? I would not say that's gonna happen really fast, because you have very strong stakeholders in the market, like physicians, pharmacies, and I don't see that we're moving so fast in such a consolidated framework like you would see in the U.S..
There's a couple of things to think about. I mean, clearly, Europe doesn't have things like a PBM. I mean, it's a completely alien concept. To Rebecca's point, it's highly diverse, different reimbursement systems. Governments have under no desire to harmonize that. Where you clearly have harmonization, regulatory, licensing, which actually we can play to that synergy.
The other thing that's worth thinking about in Europe, you know, when I first started in this industry, someone told me: "You only need to know three things to run a generics company, be the cheapest, be first to market, and have the best supply chain." Now, reality, it's the relationship between those three things, and the Indian players, particularly, generally are good at being first to market and generally have low cost, yet they have no presence, really, in Europe, paying less than five, six, five, six points of share.
Six.
There's something else going on, and I think that's really what Rebecca explained, is that the relationship with the market, how close, you know, your proximity to your customers, making your portfolio. If our German business feels very German, our French business feels very French, and that's such an asset that our competitors just really struggle to get that kind of scale. The economies of that scale really flow through. When we launch more products, we don't need more infrastructure. It just flows through the organization. It's something that's very, very different between the U.S. environment, which is generally, you know, a different kind of framework, and then the European one. Keren?
Yes, I also had a bit of difficulty, but I think you asked on price erosion going forward. That was the question? Yeah. I'll not try to guess pricing in the market. I would say that definitely, as you're well aware, there is price erosion for both, you know, small molecule and biosimilars in the U.S.. I would say that it's the regular part of the business. I would look at it as usual as business as usual. You know, you talked about the cycles, so definitely we've been through a difficult cycle, and I'm very optimistic. We need to remember that market do not erode, it's the specific products that erode, right?
If I look at our portfolio, I can tell you that we are very confident that we have enough launches to offset the erosion that we're gonna see in the market, both in the small molecule and the biosimilar, and we expect to significantly grow going forward.
Okay.
Thank you. I have two more questions. on For Europe, could you run through the example of Rixathon, what happened there? When we looked at the prescription data, you were second to market, you quickly became the leader in Europe, which I guess is a more diversified, tougher place to succeed, and then you moved into Europe top five and did incredibly well. Now you're number one. I was just wondering, you mentioned how commercially Sandoz and Novartis have been operationally distinct. I can imagine having Novartis as a parent company with an oncology portfolio may have helped at some level in terms of commercializing and developing Rixathon. The second question is along the same lines, but maybe for the U.S..
If you look at these hybrid companies that are pharma and generic companies, who can offer a portfolio of products across both RX and BX and GX, is it an advantage having broader contracting just outside of sort of generics and biosimilar operational setup? I'm just thinking of a company like Amgen, where they have obviously, they're present in biologics, they're present in immunology, they have both brands and generics. Does that give them an advantage versus you? Or is it just, you know, there are different strengths and weaknesses for the two different business models?
Shall I start? Yep. Thank you. Thank you actually for the question because I didn't have the chance during the presentation. It's a very important point, both in Hyrimoz, but also equally in Erelzi. Nevertheless, if you look now, Hyrimoz, which I presented, 19 markets, we're number one. It's pretty similar if you look at Erelzi, right? There must be something which we're doing well, and I would put it back to the platform we're having, but then the commercial capabilities. In this case, this is absolutely critical to win. It's this ability to really have this deep customer understanding, our contracting pricing excellence, and then the team in the market who really pull into deep customer understanding. This one, I would really pull.
I said, this advantage of having a separation, I would not link it to the Novartis oncology portfolio, because if you think about Arelzy's immunology, right? I would have other examples with Omnitrope. I mean, we have different examples where we prove that we really have these commercial capabilities to know how to play, know how to win across market archetypes. It's across all the markets, so it's not a single market, it's across. The people in the teams in the market is a really key success factor and differentiator for Sandoz.
Keren?
Yeah, thanks. Look, on the pharmacy benefit, that's where you kind of refer to, there is an advantage to have a portfolio, right. When you are negotiating with your payers in the U.S. In the medical benefit, it's very different. I would say that the way we look at it, you know, we don't have the portfolio of an innovator. What we do have is a very broad portfolio across different, you know, therapeutic areas. You know, payers have a lot of respect and commitment to work with companies that are bringing those products into the market. We don't have this innovator approach of, again, replacing the brand or bundled products. We do working on a very broad portfolio, and we believe that we have excellent relationship with the payers and will continue to be successful in bringing those products to the U.S.
Yeah, sure.
Maybe a question for the international markets as well, given everything explained to U.S. and Europe. Could you help us understand for biosimilars, the relationship between price and volume? I'm just sort of thinking that as prices come down, volumes might accelerate relative to where they were before, thinking about affordability and things like that. We've seen examples where, you know, I guess Glaxo with antibiotics that reduced prices in, historically in Asia, and they gain more volume share and they get, you know, sales overall went up from a mix of, you know, volume going up dramatically versus prices coming down. I guess we took something like Avastin, for example, in your regions, where the split between adjuvant and metastatic in the U.S. might be 2/3, 1/3.
I think it's the other way around in your regions, and so as prices come down, presumably, you know, the use in the adjuvant setting, which comes with a longer fixed term, could potentially go up, so volumes go up in the response to prices coming down.
Good. I understand the question is related to the biosimilars in the rest of the world, especially in countries where the price could be with high erosion over time. Is correct?
Exactly.
Yeah.
Prices coming down, so open access to drive volumes up.
Yeah. Thank you for the question. I think that's an interesting one. It's part of the way I was presenting today. In some countries where we understand already in advance that this is going to happen, eventually we decided not to play. We basically allocate resources, effort, promotion, and our volumes to the countries where we see more predictability. The case of Brazil, this is a perfect example, we understand exactly what's going to happen in the next 10 years. In other geographies, within Asia, we have a very predictable environment in Hong Kong, but we have obviously a different pricing versus others, but it's predictable over time. We have a 2- 3 years agreement, so this is a way of the way we approach this pricing.
Where we get long-term, sustainable, attractive price versus where we get a lot of volatility, we eventually decide not to play. That's part of my presentation. We decided not to play in some geographies because they are not either reliable, attractive, or long-term.
I think if you look at the region, you've got markets like Australia, where we're really driven by similars. Japan, you know, we have a strong platform. You've got sort of more regulated markets that are much more like Europe and the rest of the world. Markets like Brazil, where we have partnerships with the government through PDP structures, you know, we look at then working with government to open up a market. Clearly, your argument is fair, you know, in terms of by bringing down the price and affordability, there's a volume expansion.
Yeah.
You've got everything in between. I mean, a lot of markets, some of the smaller ones, originators may not have even launched, so they're fairly small volume, but good margins. It's interesting you talk about the antibody business because I used to run that franchise, and a lot of that actually was about promotion. It was about actually positioning it. In India, it's the world's largest market for clavulanic acid, but it was about the brand promotion rather than getting the right price point, but not necessarily the cheapest price point. I think that's really the strategy that we've taken with international is, we're not promising to be the cheapest. You know, we're you know, we're high quality biosimilar, but it does open up markets at a different price point to the originator.
If you want, I can give you billion on Richard's comment, specifically the case of Australia and Japan. We're talking about in Australia and Japan. In the case of Japan, we have a 70% market share. In the case of Australia, we have an 88 by market share. That is the share we have in the market in the last couple of years since we launched.
Thank you. I think we're at time. Thank you so much for your questions. We now have a one-hour lunch break, and we're back in exactly 1 hour now from now, if that's okay. Thank you so much.
Thank you, everybody. Now we'll get into the operational part of our journey. Really, I want to sort of reflect on three areas. Pierre? Pierre heads up as the Chief Commercial Officer. In his role, he's responsible really for the end-to-end platform, identifying our pipeline, working with Claire and Glenn to ultimately realize that and then bring that to the business. For the last three years, Pierre has headed up the biologics organization, so a lot of the expansion that we see today is really down to the hard work of Pierre and his team. He's had 20 years of working at Innovative Pharma, Alcon, and Sandoz. He'll come and talk to you really about how we define and drive our pipeline. In terms of developing our pipeline, I'm delighted to introduce Claire.
Claire is our Chief Scientific Officer. She has a distinguished career in both originator pharma, but also in generics pharma, and has really transformed the development organization within Sandoz. Lastly, but not least, we then look at the supply chain and the operational opportunities that we see, both to deliver and support our pipeline, but also to expand our margin as a business going forward. Glenn will take you through that. Glenn joined us about a year ago. He has, you know, many decades of experience in innovative, generic pharma in many geographies around the world, and we're delighted to have him as part of the team. With that, Pierre, the floor is yours.
Thank you, Richard, and hello, everyone. It's really a pleasure to be here to present to you today. As Richard said, I've been with the company actually for 21 years, or the group of companies across Novartis, Alcon, and now Sandoz, and I've had the privilege of working across biosimilars and generics. In this role, I cover pipeline strategy, portfolio operations, key launches, M&A, licensing, divestments, and other key global commercial functions. What I'd like to do is begin with the big picture, big picture summary of this morning. Richard talked to you about the very unique position Sandoz is in as a scaled global leader across both generics and biosimilars.
The region heads have presented to you on our excellent commercial platforms and how we lead with market proximity, launches at LOE, and having portfolio scale, so the right portfolio in the right area. I'm gonna build off those two elements and share with you, looking forward, three main areas. What's our strategic framework for pipeline management and definition? What is our highlights, if you will, of our, both our generic category and our biosimilar category in terms of pipeline? Last but not least, what is the launch value outlook over the next five years, and why are we so excited about that potential? Moving to the strategic framework, this is very critical and will flow through the next slides that I take you through. It's very critical for us in terms of value delivery and operating process.
I'm gonna highlight a few additional highlights that are here, a little bit more than what's beyond this slide. If you look at the selection frame, what I'd like you to take away from this element is that Sandoz is a company that has built a pipeline for products that will launch at LOE. That is incredibly important to highlight because those are what will drive the most value for us, and you've heard all the reasons why from commercial platform presentations. In essence, to be very clear, we will not be pursuing building a pipeline of launching products that are already existing in market with many generic competitors. We will do the opposite. We will launch products and majority build for products that launch at LOE. Second aspect is the commercial lens.
You heard about the distinct differentiation of the Sandoz commercial capabilities and platform. That's very critical because that commercial platform is ultimately used and leveraged in all our pipeline process and governance boards. We get our insight direct from business leadership, who are included and involved in all reviews and decision-making on pipeline. Ultimately, for the simple reason that what we build in pipeline, we want to ensure we succeed when we launch in market. The other area that's really important to point out is scenario evaluation. You're gonna notice through the presentation that 70% of Sandoz's pipeline is geared towards complex generics and biosimilars. That means we are selecting programs 7-10 years before they launch.
Having very good line of sight on intellectual property scenarios and really good line of sight on what product do we need to develop now, so that 7- 10 years from now, that is a winning product on day one of market formation. Last but not least, the two areas of technical lens. My colleagues, Claire and Glenn, will present to you in the upcoming sessions, and their expertise and advisory is critically important, where they hold decision rights and have presence with their teams across all our boards, not only to ensure that we have conviction on the pipeline that we're developing, but also that we have clarity and alignment on network strategy, capabilities, and the efficiency that we can drive with that. Last but not least, I want to bring to your attention the overall point of the operating review.
We have a very high level of discipline and diligence with monthly operating reviews, including all presenters that you have met here today, being part of a monthly executive governance forum on both pipeline and launches. Overall, this really, for us, sets a very confident tone on the next slides that I'll present, and why we're so excited about the pipeline that we will deliver. Clearly, the big picture is that we're moving to a more complex phase of delivery of pipeline assets across both complex generics and biosimilars. We have a very broad pipeline, as Richard pointed out, more than 400 generic programs and 24 biosimilars in the pipeline.
It's important to point out that this mix shift, with 70% contribution from higher and more complex technologies, is ultimately going to allow Sandoz to grow, but also to mix shift and to provide even more value with the launches ahead. What I'm gonna do now is spend a little bit of time on the generic pipeline, afterward, followed by the biosimilar pipeline, with a view of the key launches that are coming up. On the generic side, clearly, we're very excited to have complex generics that are covering $44 billion of loss of exclusivity out of a total portfolio of projects of 400 projects covering $145 billion in LOE.
Before I speak a little bit more on complex generics, I'll explain to you our approach for standard generics, where we have a very disciplined and focused approach. When we look at standard generics, we see a few lenses that are very critical. We target high-value assets in market. We target launching at LOE in those asset categories. Last but not least, we look to maximize scale in those asset launches. Let me give you a live example of a product that we launched only three weeks ago. There's a large product called Forxiga. Forxiga is an originator brand with more than $4 billion a year in growing sales in the diabetes space and is an oral product. We developed a generic.
We launched on day one in the Canadian launch to ensure that we're in a position at market formation so that we can succeed. We're gonna scale that launch globally across Europe, the U.S., and international markets over the next 3-5 years as market formation occurs. Here you've got a great recipe of going after value, going after scale, and being there at day 1 in all the key geographies, leveraging our internal development and manufacturing network really efficiently. Now, moving to complex generics, where clearly with 1/3 of the value contribution and $44 billion in LOE coverage, this is a very important strategic segment for Sandoz. We've a multitude of different technologies here, covering complex high-dose injectables and IVs, complex peptides, drug device combinations, and oligonucleotides.
Some of these are emerging technologies that will only see the LOE pattern occur 2030 and beyond, but it's very important that we have the capability and the early planning to succeed here. My colleague, Claire, is gonna present to you on our capabilities in this segment, in the development section, as well as real examples of highly complex products that we've already launched in market and succeeded on. Now I'll switch to biosimilars, where I want to point out a few important facts. Bring you back to Richard's earlier presentation. Today, Sandoz has eight in-market biosimilars, they are generating $2 billion in annual sales with a very healthy growth rate behind them.
What we're really excited about is then adding 24 additional biosimilar launches over the decade to come as part of our pipeline execution, and really putting us in a position to be the undisputed industry leader in this category. Clearly, it's a complex category. It's a category where you're planning 8-10 years in advance. As we look at the cost, concentration, and the planning, we look forward many years in advance to understand what product are we developing, with what features and benefits, and why will we win 10 years from now in that category? I'm now gonna show you the four upcoming launches we have, and it hopefully give you some examples of how that strategic process has played out into winning proposition for the upcoming launches.
Here's the big slide on the global launches, the four major biosimilar launches that are going to occur in the next few years. Let me start with the first product, adalimumab, which is a reference biosimilar to the originator of Humira, covering a very large LOE of value and a total value of $21 billion globally. Clearly, this is a very competitive field, and Sandoz is in a very strong position of already having had FDA and EMA approval for the high concentration formula. A few things that are really important for you to know about this launch. As my colleague, Keren, pointed out, first and foremost, we have a high concentration formula. Why is that important? Because the originator has shifted 85% or more of its volume from its low concentration formula to high concentration formula.
So far, only three companies have an approved high concentration formula offering, Sandoz being one of the key companies. This is a really critical point. Second aspect that Keren mentioned is ex U.S. supply, reliability, and record of excellence. We have five years of supply reliability information across being number one in Europe, number one in markets like Australia and Canada. The confidence that that can transmit to U.S. customers is unparalleled in terms of our ability to ensure that we will be positioned as a partner of choice and a good strategic partner for not only the short-term rollout, but the long-term rollout of the launch. The other aspects that are potentially unique and really interesting for you to know about are two aspects. One is that we have a very unique device, and it has some important differentiating features.
First and foremost, it's an ergonomic design, so it's got a triangular design, which for rheumatoid arthritis patients, is very helpful and very much appreciated by customers and not offered by all companies in the segment. The other aspects of the auto-injector include a large viewing window, thin needle gauge, as well as a double-click presentation feature. What does this lead to? It leads to real-world evidence in the last five years that this is a best-in-industry device, again, can ensure customers that when they transition patients from the originator, they will have an equal or better experience on the device compared to what they had prior. Last but not least, on adalimumab, one very important differentiating feature, we will be one of the only unique companies to have a starter pack.
Now, this was part of our strategic planning several years ago in anticipating that customers may not only want to transition existing patients, but may want to obviously start new patients. If Sandoz had a starter pack, we may be having a unique offering. We will have that at our U.S. launch, and we anticipate that this might be a differentiating feature for the company. Overall, very large LOE, and I would point to the fact as well that the high concentration formula will be rolled out ex-U.S., where we already have a leading position in a business that is growing double digit, as you heard from Rebecca, over the last year, and we have a leading position. A great asset, very confident on our position.
Okay, now moving to a very different launch and a very unique one with Natalizumab biosimilar, a proposed biosimilar to the originator, Tysabri, used in multiple sclerosis, with global sales of $2 billion, largely split, $1 billion in the U.S. and $1 billion ex-U.S. This is a really exciting and unique opportunity where we expect to be first and potentially alone in the market. We don't see anyone initiating clinical trial activity, we at least feel very confident that for a two-and-a-half to three-year window, we will be the sole entrant in the market. Very exciting market for a few reasons. You know that the MS market, multiple sclerosis, has been growing for many, many years, but it's also seen a lot of innovation disruption. Many new therapeutic agents have entered the MS space in the last decade.
What's really interesting about Tysabri is despite all the innovation disruption that's occurred, Tysabri has largely held a 10% share in most major markets. It's really well-positioned as a high-efficacy treatment used in patients with highly active disease in a second and third-line setting, and we look forward to bringing a biosimilar with all the attributes needed by patients and customers to be able to succeed. The next really exciting launch is denosumab, the third line that you see on this graph, a biosimilar proposed to Prolia and Xgeva, filed already in Europe, the U.S., and Canada. Here I want to point out a few things. When you see the $7 billion figure, it's important to point out that two-thirds of that revenue base is in osteoporosis, and that's seen continued growth over the last several years.
This is a twice-yearly injectable in osteoporosis, and this is gonna build on a point that Richard brought earlier. Richard explained to you that when biosimilars come to market, they can greatly expand the original position of the originator brand because of more accessible pricing. Here, only 15% of patients in public healthcare markets today, such as the EU5, have access to denosumab. We see the potential for really significant market expansion to be able to bring this therapy to more patients with more accessible pricing and the great commercial platform that we have. Last but not least, we have an aflibercept biosimilar program to reference medicine EYLEA. This will see a readout of the phase III clinical trial in Q3, upcoming shortly. We're excited for this space for a number of reasons, and I'll bring you back to the strategic framework here.
Several years ago, we identified that this would be a very competitive market at entry. We determined that ensuring that we could launch with a prefilled syringe, in addition to a vial offering, would be very important to our success. Now, it's important to point out that the originator brand has a prefilled syringe. It's more than 80% of their revenue. It's a very high technical hurdle to achieve FDA approval for the prefilled syringe. In fact, the originator brand faced a CRL and a delay in bringing their brand to market when first attempted. We are leveraging a platform of an already approved prefilled syringe technology across both development and manufacturing. We feel really confident to enter this market with a winning target product profile in a market that is large and growing.
Hopefully, this gives you a sense of four great examples, leveraging our strategic framework to ensure that we're launching biosimilars, all of these at market formation, and all of these with differentiated and or highly competitive profiles to ensure success and ultimately winning conditions for Sandoz with customers and patients. Wrapping up to my last slide, here's a great summary of why we're so excited about the pipeline. You're gonna see here on your left-hand slide, aside, that in the last five years, Sandoz launched $1.6 billion in value in terms of new launches and medicines. The makeup of that was approximately one-third biosimilar. Look forward to the next five years on the right-hand side of this slide, and we have nearly double the pipeline potential value already in our existing pipeline.
In addition to that, you see a mix shift in line with our strategy of having approximately 50% contribution from biosimilars and having a higher proportion of complex generics, contributing 35% of a contribution in the generic space. We're really excited about this pipeline, really excited about the future, and with that, I'm gonna pass to my colleague, Claire, who's gonna take you through our development network strategy, capabilities, and operations. Thank you very much.
I will start by introducing. I'm Claire, as already spoken. We have had 35 years in pharma, always in R&D, the first half of my innovative and the last half, I've spent 15 years in Teva, working extensively on the generic portfolio, specifically in complex injectables, and the 10 years I've been with Sandoz since October 20. Pierre has taken us through a very eloquent description of a deep and wide pipeline, biosimilars, and small molecule generic products in it. As a scientist, I'm truly excited to have the opportunity to find my passion for science, people, and being able to get products into patients' hands.
I want to take some time with you this afternoon to take you through the Sandoz Global Development, which is an organization that sits at the heart of Sandoz, and is the engine that really drives the growth of Sandoz as we move forward, delivering the current pipeline and also delivering the future. You know, I've already said that I've spent time in innovative and generic R&D, so that gives me a very unique perspective on what a generic mindset truly is, and the opportunity that we have as we separate from Sandoz to really optimize that generic mindset, build agility into the way that we look at cost optimization and speed of development, and most significantly, lean into our regulatory and IP capabilities to create competitive advantages for Sandoz in the market, create greater access for patients our products.
I wanna give you an introduction to the organization, which is a development and regulatory organization, where we have 1,700 skilled, highly experienced, scientific, clinical, medical, and regulatory associates, very passionate about delivering the portfolio. They are located in our six development centers, which is a quite cost-efficient footprint, and it's really important to recognize that we are well-equipped in terms of our infrastructure, in terms of our capabilities, in terms of use of digital tools to accelerate the development process. That has led to both in the past and moving forward, our very strong track record of success in getting products to markets. I'm particularly proud to say, and as Rebecca has already said, that we have a 100% success record in bringing biosimilars to market, and we are very smart in our clinical approach.
I'm particularly excited about the fact that we have small molecule generics and biosimilars under the same. From a skills, a capability, and knowledge point of view, there's a lot of synergy between having the two together, and I think it makes it smarter in the way that we work. Some key examples that, you know, Pierre has shown you, the device for our adalimumab product, our device development capabilities, a platform that's common across our complex injectables and our biosimilars, as well as our regulatory knowledge and the need to do analytical characterization is something that we can tap into and take advantage of for both parts of the board.
Generic industry continues to be a very rapidly evolving and challenging one, and the fact that we have highly skilled, very experienced regulatory associates that really know the regulatory requirements in each market and are able to lean in and work very closely with regulators to shape the regulatory landscape, continues to give strategic advantage to Sandoz as we bring new products to market. Lastly, the last point on this slide really is recognizing the breadth of technology and the span of our pipeline. It's not practical to expect that we can do everything internally, both from an infrastructure capacity point of view, but Sandoz, because of its scale, reputation, and credibility in the market, is actually a very desired partner, and we work with high-quality external partnerships to succeed in delivering our entire portfolio.
Keren, Rebecca, and Paco spent time this morning taking you through the commercial platform. We are really proud of the development and regulatory organization and the track record it has in generic. In each of the markets, which have their own complexity, Europe, over 40 countries. Paco's already spoken about selectively playing in 26 countries, in America and in Canada, recognizing that we have 1 regulatory capability to understand the development needs, regulatory landscape, and the IP landscape for these have allowed us to be able to bring over 120 unique submissions in Europe, a similar number in international. We've been very assertive in increasing the number of files that we've put into the US, working collaboratively with Keren to bring the rebalancing of the U.S. profile as we move forward.
Another part of our key focus as a development organization, being very assertive in our first to market strategy. You know, we say you have to be first, you have to be first, you have to be first, and you have to be fast with respect to generic. Again, for our European countries, over 80% of our products are launched first to market. In the U.S., we have increased the number of first-to-market launches that we have, and I'm particularly proud in international, where we have moved from 10%- 25% first-to-market opportunities in the last three years. That is a profile that we will continue to do, and we continue to work very closely with our commercial colleagues to ensure that we're meeting the needs of the market, both present and future.
That is well showcased as I show you some examples of our complex generics, which Pierre mentioned earlier. Taking a step back, you know, one of the things that tempted me to come to Sandoz when Richard approached me 20 months ago, was the fact that Sandoz was first to file with ferumoxytol. They then succeeded in getting it to market, and that really tempted me as a scientist and as a professional because I thought, "Wow, there's some serious capability in this organization." They were able to bring this because it's a complex API, it's an iron-based product, which is then developed into a solution formulation.
The analytical characterization requirements for that product and the very high barrier of clinical requirements that the FDA have posed to get approval and to get to market, was something that Sandoz was capable of succeeding with. Similarly, there are two examples there, fulvestrant and albuterol, where the drug device combination capability and the fact that we have invested in a device organization, really showcases a very established capabilities in the organization to do that type of product, but also for future technologies, the capability to continue to meet drug device combination products. Lastly, the last example there, which is transdermal, which is launched in Europe. bupropion, again, has its own complex and regulatory requirements. This platform of capability and understanding of the development and the regulatory requirements. You can't hear me? Oh.
Means that we have been very successful in the past, and that's a future platform for future successes. In combination with that level of capability on the generics, we already have a significant success record in bringing biosimilars to market. We've already heard about the eight biosimilars that are in Europe, where we have number one position in five of them. That pioneering spirit of Sandoz in being the first to bring a biosimilar to market in Europe, Japan, and Canada, opening the U.S. market, particularly excited about the planned launches that we have of the four molecules that Pierre has already shared with you.
That increased success rate of understanding the development timelines, which is 5- 9 years, the cost of development, the speed of development, and the ability to shape regulatory guidance, create advantage in the market for biosimilars, gives me significant confidence that for the remaining 24 products that we have, 16 in early development, 8 already under clinical and regulatory review, we will succeed in bringing those, and that will underpin our growth as we move forward. Just taking a step back, and I really want to talk about the key technologies and some of the end-to-end development capabilities and how everything works together across the organization. The development organization has the capability to deliver every technology platform, but focus is so critical. We focus on four, particularly biosimilars, oral solids, injectables, and respiratory.
Working in an end-to-end manner with Pierre, to understand what assets we're gonna be working on, with Glenn, to ensure we have a good understanding of the manufacturing infrastructure in which we have to develop and manufacture these products to be able to launch successfully. That end-to-end approach is something that we work on in a very smart way. Similarly, when we look at our development aspect, you can split it into several areas. There's the early development around analytical and formulation, the later phase around the clinical and regulatory. Launch. We've been very specific and strategic in vertical integration and deciding where to play and where not to play. Specifically for biosimilars, we have our own drug substance development capability, similarly for anti-infectives.
However, for our small molecule generic portfolio, we took a decision that we would partner externally with API suppliers, which gives us access to API early. It allows us to bring the products to regulatory review first to first to file, and later on, be first to market with these opportunities. Similarly, that regulatory and IP framework is a key part of understanding what our development strategy is. Working very closely with our IP and legal team, we're in the business of busting patents. You know, that's what it means to bring products to market at loss of exclusivity or even before loss of exclusivity, when we were able to work in such a way that we were able to bring the right formulation early on.
Our capabilities and our people sit in six development centers, which are highly equipped, both in terms of equipment, but also in terms of digital capabilities and the use of artificial intelligence, which we have started to lean into quite significantly to accelerate the time of development. There's a strong strategy around the design of our network, both from a point of view of access to talent, but also from the point of view of cost optimization, in having some of our centers situated in low-cost economies, as well as ensuring that we can actually find a balance between talent and cost. Our oral solid, which is primary base for our generic portfolio, is actually based in three locations. We have our injectables based in two: simple injectables and complex injectables.
I spoke about previously, that there's actually a lot of synergy between the complex injectables and the biosimilars. Because of that, you will see that we've centered Kundl and Ljubljana as the place where we will be building our biosimilar capability as we move forward. Another key area for us is the respiratory space, where, again, we have end-to-end capability, both in terms of development and manufacturing, in having both capabilities located at our Rudolstadt site in Germany. Complementing our development centers, we also have centers of expertise where we focus on key topics which are of significant interest to the regulators. Nitrosamines has been a key area of focus in the past and will continue to be a key area of focus.
Being able to understand how we do biosimilar analytics and also something like leachables and extractables, again, has been a very key area of focus from our regulators. We complement our internal development centers by having centers of expertise for knowledge-sharing, best practice development. In parallel with our highly skilled scientific community, we also have a highly capable regulatory team, which shapes the industry landscape through advocacy and scientific discussion. This is particularly important. You know, we spoke about we have a current pipeline, but we continue to do significant industry intelligence on what technologies are coming our way. For some of these new and emerging technologies, the regulatory guidance's have not yet been defined.
Actually having skills and capabilities in regulatory, where we're able to speak into the scientific guidance on complex products, define and work very closely with the regulatory agencies to shape the clinical programs that are required, and also build on the guidance's for analytical similarities through representation from our subject matter experts on some of these industry panels, like AAM, Biosimilars Forum, et cetera, continues to create a competitive advantage for Sandoz and has been part of the reason that we've been able to succeed in the past with being very smart in how we leverage our products into all the markets globally. Similarly, recognizing that synergy, again, from a regulatory point of view, we've integrated our regulatory teams across generic and biosimilars.
One of the changes I've made to the organization, recognizing the strategic importance of regulatory, is I've brought one of our leading regulatory leaders into the organization to again speak to this particular area. I've already shared with you our internal capabilities, and maybe to sum that up, I think we have a lean, efficient, highly skilled, very experienced organization of scientists, regulators, clinical, medical, patient safety, that sit in our six facilities. That is complemented by working very closely with high-quality external partners. Again, I said that, you know, we cover such a range of technologies, we don't have the infrastructure to do everything internally.
Glenn and I have worked very closely to define what our technologies platforms are, where do we play internally, both from a development and manufacturing point of view, where we partner externally to allow us to have access to technology, capacity, or people and expertise. I'm particularly proud of a recent relationship that we've established with Just - Evotec, which I think is very disruptive in the biosimilar space, which gives us access to the artificial intelligence capability to deliver and develop drug substance for biosimilars, which will then be put into their continuous manufacturing framework. Just - Evotec is an organization that works very closely on early development with several innovative companies, and they have already started conversations with the FDA on acceptability of their continuous manufacturing platform.
We are highly confident that we will be able to succeed in delivering many of our products with this Just - Evotec relationship. Similarly, we will continue to have that relationship with Novartis, who currently are working with us on execution of some of our technical laboratory work in some of our existing biosimilar projects. I'm very confident that, you know, we have a strong base as a development organization to continue to deliver our portfolio, both the 400+ generic molecules we're already working on, as well as our 24 biosimilars. We continue to have the breadth of capabilities to cover the full range of technologies in every discipline within our organization.
We will build on that strong track record of success, and we will continue to work exclusively and extensively with very strong external companies, partnering with them to ensure that we can have access to a flexible network, both internally and externally, to deliver our current portfolio, but more significantly, to continue to pioneer and deliver new technologies for our upcoming portfolio as well. Thank you. I hand over to my colleague, Glenn.
Thank you, Claire. Good afternoon, everyone. My name is Glenn Gerecke, and I lead Sandoz Manufacturing and Supply. This means that I am responsible for delivering all of the products that our commercial platform heads discussed with you earlier today, as well as all of the development products that Claire and Pierre just discussed with you in the last two sessions. That also means that I am responsible for delivering 350 basis points of core EBITDA improvement over the time period between now and 2028. I'm going to take you through exactly how we are going to do that. It is perhaps useful to look at the organization as it was at the end of 2022, so that you can have a basis for understanding what I will talk about as we go forward today.
I selected some numbers, and I selected some data for this slide that I believe are really differentiating for Sandoz, and I will take you through some of that. The first is 160 regulatory inspections of our facilities over the last 4 years without a critical or major observation. This is differentiating in our industry. It speaks to the way we run the network, and it speaks to our ability to continue to deliver these high-quality products for years to come. It's a basis, and it's fundamental in our operations. The next number I'd like to show you is 90% of our products delivered on time and full in 2022. Given such a broad net array of inline products, this is really an incredible accomplishment.
This means every line item on an order delivered the day it is supposed to be delivered, 90% on time. I will remind you, this is coming out of the COVID era, when supply chains have been extraordinarily stretched. 1.7 billion packs delivered in 2022 in a very asset-light network, only 18 manufacturing sites. I think you will find this to be quite differentiating when you look at large-scale generics. I will talk you through why I'm so extraordinarily proud to lead this network. When Richard asked me to join Sandoz, partway through last year, I gladly did join, but I did not know all of this information. When I came to the company, I became incredibly impressed with the way that Sandoz Technical Operations has been operated.
It gives me tremendous confidence to know that going forward, we will be able to build on this success and execute the plan, which I will describe for you as we go on today. We said that we would move the company in 2028 to 24%-26% core EBITDA margin. We said that 350 basis points of that EBITDA margin would come from operational improvements. Those operational improvements fall into four categories. They are design of the internal and external network, focused vertical integration. This is vertical integration where it makes sense, and there are some places it does make sense, and there are some places it does not, and I will take you through that. Operational excellence. Operational excellence, I define, as getting more value out of a given asset base.
We have a long history of operational excellence, I'll explain to you how we will take it forward. Finally, external spend optimization. These four levers put together will deliver that 350 basis points of core EBITDA margin improvement. Let me start with the internal network. You can see that the internal network is composed of 18 different manufacturing sites. I would characterize this network, first of all, as being highly utilized. We are getting extremely good value and volume out of quite a limited fixed cost base. The network is also characterized by well-maintained facilities, very modern equipment, a group of colleagues that operates this network that is not only well-trained, well-qualified, but most importantly, highly engaged in our business.
The network is capable of making all of our oral solid products, in addition to the complex generic products that Claire described to you, and biosimilar drug products. If you look at the left hand of this particular slide, you will see that we have reduced the size of this network by seven sites over approximately the last five years. This does a couple of different things for us. The first thing that it does is it limits our fixed cost exposure going forward. The second thing that it does is it limits the amount of maintenance capital and recapitalization that we need to do going forward. All of this leads to cost competitiveness and cost efficiency. I will point out to you that this network has changed, although the volume output has increased.
Let me talk now about where we will go with both our internal network and our external network. You see on the left-hand side of the slide, just staying with the internal network a little bit longer, that we have already announced that we will reduce over the next couple of years, three more sites. Again, limiting fixed cost exposure and limiting the amount of CapEx that needs to be put into our internal network. As a general operating principle, we manufacture internally where we believe that we bring competitiveness, and we bring differentiation. We look at each of the technology platforms that Claire described to you earlier, strategically, and we look at each of the products in the portfolio from a business case perspective, and we decide, will we manufacture internally or externally?
Always through the lens of: are we the best at this, or potentially are external providers better than us in a particular technology or with a particular scale or with a particular portfolio? Let me bring us now to the external network. You see that we have 700 external supply points today. This is part of an asset-light philosophy, and this is part of a maximized value philosophy that we have in Sandoz. Of the 700, a little more than 200 are actually active pharmaceutical ingredient suppliers. As Claire has said, we choose the active pharmaceutical ingredient supplier who can allow us or enable us to be first to market, first to launch.
We then often switch API to do life cycle management of our products, to make sure that the products are kept competitive, with API being a very large part of the product cost. We rather like having 200 plus suppliers. It enables us to be very flexible, it enables us to have very little fixed cost, and it enables us to make sure that we keep this market competitive for our good and for the good of our customers and our patients. The other 400 or so plus sites are actually finished dosage manufacturing sites. Here is an area where we believe we have tremendous opportunity.
The idea with this part of the network is that we will concentrate our external spend with suppliers, where we can build strategic relationships, win-win relationships, and actually very much improve our competitiveness for the finished dosage side of our business. I think it's important that I speak with you about Novartis as an external supplier to Sandoz. As we spin Sandoz away from Novartis becomes a CMO. The main message that I want you to remember from this slide is that we will sign agreements with Novartis that will enable us to supply all of our in-line biosimilars and all of our near-term launch biosimilars, as they were described by Pierre. Novartis, over the years, has shown to be a highly reliable, a very high-quality supplier of biosimilars for Sandoz, and this will continue.
In this agreement or in these agreements that we will sign. We will also be able to maintain a highly cost-competitive position that will give us the commercial flexibility that we've been talking about so far today. Of course, we will look to diversify away from Novartis over time. We have already mentioned Just - Evotec, so manufacturing tends to follow development, and while Just - Evotec gives us tremendous development capability with a brand-new technology platform, it also gives us the option on this very same manufacturing capability. There are other examples which we'll bring to you at a later point in time. Staying with biosimilars, now let me shift gears a little bit into where we do wanna be vertically integrated. Richard has already discussed, and you've already seen our press release, that we will build a biosimilar drug substance facility in Slovenia.
This is a fully end-to-end, fully integrated biosimilar drug substance facility, starting with cell bank management, through manufacturing, through quality control, storage, and distribution. We will begin construction late this year. We will complete construction and have the facility ready for technical transfer in late 2026. Key point on the slide is when this facility is built, and we are ready to transfer products into it gives us a step change in cost competitiveness, even over the Novartis network, which I've mentioned to you earlier. I'm going to stay with focused vertical integration, and I'm going to bring you another example, and this is in antibiotics. We've not talked about antibiotics a lot today, but as Gilbert mentioned in his introduction, when Sandoz introduced the first oral penicillin in the early 1950s, it was groundbreaking for the practice of medicine.
Ever since then, it's been an extraordinarily important part of our portfolio, really a cornerstone of our portfolio, and it has remained a mainstay in the practice of medicine. We are the leaders in antibiotics worldwide. We are number one in value, and we are number one in volume, and we have continued to invest in this business to make sure that we remain number one in cost competitiveness. This $250 million that we've invested and, you know, over the years, will enable us to make sure that our network remains the best in the world, fully integrated and fully in Europe. Most of this money has already been spent. Two of the three sites that I said we will be closing on a previous slide will be a result of this investment.
You get an idea of how we continue to develop our network. Next, I will move to operational excellence. Operational excellence, getting more value out of a finite set of assets. I've mentioned to you our strong foundation in terms of quality, in terms of reliability, and I would add, in terms of safety. Operational excellence is really in the DNA of Sandoz. We will continue to find ways to maximize our asset utilization and to improve our processes, both the technical processes in terms of manufacturing the actual product, but also our supply chain processes. We have a plan that we continually execute. We build our challenges from an operational excellence perspective into that plan, and we monitor it constantly, and we do very well with it. We also benchmark ourselves.
We know that we're good, but we know that we can get a lot better, and this gives me a lot of confidence in telling you that between now and 2028, we'll be able to continue to deliver value out of our network. Finally, external spend optimization, procurement optimization. On the left-hand side of this slide, I show you a bit about our external spend base. We spend $4 billion externally as a company. It is spread out amongst 13,600 different suppliers. If you do the math, that comes out to about $300,000 per supplier. It tells us that we have a huge amount of opportunity to do a much better job with external spend optimization.
As part of Novartis, this has been done by a fragmented procurement organization from different parts of Novartis, not necessarily focused on what we need as a generics company. What will we do differently? The first is we will leverage our scale, and this has to do with not only the direct materials that go into our products, which of course, are a large part of the product cost, but also all of the indirect services of the company, which have largely been untouched. We will reduce complexity. This is through internal demand reduction, but it is also through business process simplification. We need to have business processes and demand that is appropriate for a generics company and a biosimilar company, not an IM company. Tremendous opportunity here.
Lastly, we have built already a fully integrated procurement organization, which is focused on Sandoz, with a brand new chief procurement officer who has selected a tremendous team. In summary, we already have a high-quality global supply network. It works really, really well, and I've showed you all the data to support that. I've also showed you that we have four main levers to drive optimization in the near term, and certainly over the period that we're covering today, which goes up to 2028. We have tremendous internal and external capabilities, through the teams we've built, the partnerships we've built to support our ambitions. Thank you very much for your attention. Richard will lead us in Q&A.
Thank you very much. Claire, Pierre, Glenn, join me. We have open up the floor to any questions.
Oh, can we not poke?
Thank you.
Thank you.
Mark Purcell from Morgan Stanley. I have three. The first one is a very broad one. Richard, you talked at the beginning about the cost of biosimilar development being between $100 million-$200 million.
Mm-hmm.
Could you help us understand that range and if the costs are coming down?
Okay.
Secondly, on biosimilar EYLEA, can you help us understand what you're doing around the high dose formulation, timelines there, IP, et cetera, so that opportunity? Lastly, the importance of cell lines. Clearly, for long-acting products like STELARA, and specifically in your case, TYSABRI, it's important to have the originator cell lines. It seems in terms of some of the things we're seeing with the regulators, so I think with STELARA, it's SP1, I think with TYSABRI, it's a murine cell line. Can you confirm that you're using the originator cell lines and provide any comments around that side of the development? Thank you.
Pierre, do you want to take that?
I can take the EYLEA high dose question, maybe to begin. On EYLEA, there are a few things to think about when we see the market and the opportunity. First and foremost, there is innovation and disruption happening in the market, from mainly from two sources. You have high-dose EYLEA that is expected to enter, and clearly, that is going to move the opportunity for patients. Instead of and kind of an eighth-week cycle of dosing, they could move to either 12 or 16, depending on a patient reaction to the dosing and the label. There's also VABYSMO from Roche, which has also extended the dosing interval and the innovation in the market. We see that in two. ways.
Number one, innovation is something we always face when we enter a market. If you think about adalimumab, it's facing competition from several classes of new immunology launches, and yet, we not only convert the originator, but we see underlying market growth as explained by my colleagues, in particular in Europe, where we have deep experience. Number two, we look at the ophthalmic market across the three primary indications, and we see LUCENTIS and off-label Avastin accounting for 45%-55% of the market in both the US and in Europe. Our view of the 8-milligram dosage for EYLEA is that first, it'll be still continue to be a very large market with an $11 billion LOE. It will face competition, but there's an opportunity to expand utilization, ultimately against the two reference agents that I mentioned.
Beyond that, for competitive reasons, I wouldn't mention any internal planning on high dose and on intellectual property. Our policy as well is to not disclose that until we have a firm statement to make.
Do you want to comment on cell lines? Do you want to comment about cell lines or?
On the cell line side, natalizumab, in particular, as referenced, is developed by our partner, Polpharma Biologics. They lead on both development and manufacturing. This has been submitted to authorities, the file itself, for both U.S. and EU. I can't comment specifically on the cell line. We'd have to engage with the partner to discuss any disclosure that we would make. What I would say is that the program itself had very good and early scientific validation with both the FDA and EMA, and we feel very confident about the filing status.
Sorry. It was a $100 million-$200 million cost, average cost of a biosimilar. What defines that range, and is it coming down?
Mainly the cost of the phase III clinicals. Now, clearly, it's encouraging that you're seeing the regulators, particularly the U.K., now start recognizing, you know, an enhanced data package rather than necessarily that. Really, the bulk of that cost is the originator samples in order to do those studies. Clearly, we see opportunities to see those costs coming down. Pierre or Claire, you want to comment?
Yeah, I think, you know, we have been working collaboratively with the regulatory agencies to be smart about the design of the clinical programs for as long as there's a requirement for clinical programs. Ultimately, we'd like to be able to influence that analytical characterization and similarities enough to eliminate the need for these clinical programs. We also manage the cost very closely by ensuring that not just with the individual regulators, but across all the different countries that we submit, that we try to align and have one clinical program that serves all of our markets. This is the true power of leverage, and again, it helps to manage and minimize the total cost of development for each biosimilar asset.
Thank you.
Thank you. I've got four questions, I think, please, if that's all right. I'll maybe go through them more, but maybe first of all, just on the Just - Evotec relationship. Curious, are there any plans to also look at potentially using their AI technology, et cetera, to make the lower cost? Because you mentioned it was best in class, low cost, to make your current biosimilars and near-term biosimilars actually a lower cost option. Or is it purely because you sort of mentioned to develop it in the future, but is there any plan to potentially, you know, improve your current COGS? And I guess sort of related to that, the Novartis contracts that you're going to sign, are those perpetuity or is the -
You know, or how do we think about, you know, who has control there, I guess, and what your aim would be on your side with regards to those contracts? The second or third question, if you like, is you mentioned, I forgot how many it was now, but a lot of people that there are a lot of sites that are providing you externally with API. Just curious, what from your side, given you mentioned that competitors and there's a lot of issues with quality, et cetera, what do you do to safeguard, I guess, from your perspective, that given the significant number of external suppliers, that you're gonna be okay, given you seem to be quite heavily reliant outside of those on third parties to supply what you need?
Finally, curious on antibody-drug conjugates, because this is an R&D question. Clearly, potentially a massive class over the next decade. Is it an area you feel is viable? Is it an area you're looking at? You know, is it something you think potentially could be an opportunity, or is it just too complex, given the challenges on, I guess, both manufacturing, R&D, and everything else?
Okay. Perhaps if we do it this way, I'll deal with the Novartis contract. Pierre, Just - Evotec, Glenn, our suppliers, and Claire, ADCs.
Mm-hmm.
Thank you. Distribution of labor. I guess your question predominantly relates to biologic supply rather than small molecule supply. We have a, I guess, a medium to long-term supply agreement with Novartis, which we can then choose to extend over a period of time. It's a supply at arm's length, but it's a very modest cost increase over the current costs that we have. Part of the benefit of, I guess, continuing with the relationship. Effectively, at the moment, it's a 5- plus 2- plus two agreement, we've got plenty of scope, A, to extend it, and then also we'll look at tech transferring a lot of that pipeline then into the Slovenian facility once that's up and running.
I think it gives us the flexibility, it gives us the assurity of supply and the confidence in terms of our cost base going forward. Okay? Pierre, do you want to take Just - Evotec first?
Sure. Claire had mentioned that we work together on end-to-end, so I'll cover one part of Just - Evotec and then transfer to Claire for the second part. Let me speak about the scope in terms of the contract. We have eight assets partnered with Just - Evotec, these are pipeline assets, not in-market assets, where we will partner with Just - Evotec on the development and ultimately all the way through a commercial manufacturing for several of the assets. What we're really partnering on here in a shared e-economy structured deal is the artificial intelligence and data lake capability that they've built in early drug substance development scaled through ultimately being able to work then with Claire's team on regulatory and clinical strategy.
Ultimately, we will have access to their commercial manufacturing capability, which they have through their continuous biomanufacturing sites, of which they've built two for some of the select assets. Maybe I'll pass to Claire a little bit as to why is this technology interesting and attractive.
I guess just the question as well is, would we use them for our existing pipeline, portfolio of launched assets?
I'm happy to take that.
Okay.
I think for our existing portfolio of launched assets, you know, the original question from Mark around cell line. We already have our cell lines well established. We've already established all of our processes. To try now to bring Just - Evotec on board with our existing portfolio is going to require establishment of new cell lines, significant technology transfers, reiteration of a regulatory process. We would have to consider whether we need to redo any clinical programs. I think the cost and timeline that is implied there makes it prohibitive.
Okay. Very clear. Thank you. Glenn?
Yes, the question relative to our external small molecule API, supply points. We have a close relationship with these suppliers. Often they come to us through Claire's organization, and then they get transitioned to be commercial suppliers. Often they are actually, we are involved with them in the API development process. During that period of time, we thoroughly examine their quality management system to make sure that, you know, they are able to operate in a high-quality manner going forward, not just for the products they produce for us, but for their product portfolio, because it's a system of quality management. It's not product by product, by product. We have an external supply organization which manages them constantly. Okay, we do have audit rights.
This is, you know, I think, a very comprehensive way of making sure that they remain, reliable, they remain high quality. The other thing I should mention is we often, because of the way we manage the life cycle, we often have more than one source of supply. You know, we double up on the critical products to make sure that we are not left without an API source.
ADCs, Claire?
I think ADCs is a very interesting technology. It's certainly a space that we are evaluating in line with all other opportunities as part of the portfolio review process that Pierre alluded to earlier. At the point at which we take a decision whether we commit to ADCs or not, we are already confident we have the foundation capabilities within the organization to pursue that particular technology as well.
Thank you.
Hi, Umer from Evercore. I have three, if I may. First, I saw you have a settlement on a peptide, Victoza, for next year, but I didn't see much conversation in your R&D review section on that. I'd be curious why that is? Second, among the big biosimilar opportunities through 2028, 2030 timeframe, the big three that come to mind, KEYTRUDA, ENTYVIO, DUPIXENT, I didn't see much mention on that, so I'm curious where you guys stand on those. Then finally, on the manufacturing side, I see a voluntary action indicated on a Austrian facility which happens to make devices. Is that where the Humira biosimilar injector is made?
Okay. Claire, do you want to take the peptide question first?
Yeah. Yes, I mean, the GLP-1 peptides is an area of interest for Sandoz. You already alluded to the fact that we have a settlement on that peptide. It's currently under regulatory review, and we continue to work very closely with both the organization and the regulatory agencies to finalize the approval and bring it to launch.
Pierre, do you want to comment on the pipe, bio pipeline?
Yes, sure. biosimilar pipeline, we have 24 assets in the pipeline. Our policy and disclosure, which is in line with industry norm, is we'll disclose specific target assets once we bring them into clinical trial phase. Right now, you have the four near-term assets that we've described today, and as we bring more products into the clinic, we'll be disclosing them as we do that. Typically, that would occur three to five years before LOE, and we do expect to bring a few new assets to the clinic over the course of the next 12- 18 months.
Other than that, I won't comment on specific assets other than to say that clearly our position is to be an industry leader in this space. Two-thirds of our pipeline is immunology and oncology, which are the two therapy areas that you mentioned.
Then to address the voluntary action indicated, question, voluntary action indicated is that when the agency has observations but does not consider them to be critical. The company is allowed to respond, of course, in an appropriate and responsible manner, but, there's no impact on business.
Thank you.
Hey, Carson Wong, Credit Suisse. On the point that you have to prepare 7-10 years pre-launch, how do you prepare for a technology required by increasingly complex pharma pipelines while still managing reduced capital intensity with the improvement you're targeting for your free cash flow conversion? Second, can you remind us how many of your biosimilars are currently partnered? If you have to share economics, does that limit your pricing flexibility if you have to pay royalties? Thank you.
I'll take the first part, and then Pierre, second. Sorry, could you just repeat the first question again?
Sorry, what was it?
Could you just repeat your first part of your first question?
Yes. On the point that you have to prepare 7-10 years pre-launch, how do you prepare for technology required by increasingly complex pharma pipelines, while also managing reduced capital intensity with the improvement you're targeting for free cash flow conversion?
Look, in a sense, I think Claire, Pierre and the team have done a really good job of showing how we've reduced the footprint, particularly around, you know, the small molecule network. I mean, you know, a company of our size with now 15 manufacturing sites is pretty lean. I think our intention as we invest going forward, we'll invest in technology platforms where we believe that gives us a strategic advantage. Clearly, we're investing in the site in Slovenia, and similarly, going forward, if we need to invest in specific technologies, we could. You know, the partnership we have with Just Biologics would allow us to make different kind of investment decisions further down the road, whether it's into ADCs or whether it's then into the biologics pipeline.
You know, I think what's actually core to the purpose of Sandoz is in many ways, we have the scale to do those things. 15 years ago, we did that with biosimilars. You know, we should be considering doing that with ADCs and other platform technologies. In a sense, where the innovator goes, we have the scale, the technical capability, the legal capability, and the clinical capability, and then finally, the commercial capability to bring those assets to the market, that a lot of our competitors just either don't have those skills or the funding to do it.
... Yeah, on the biopartner question, clearly, there are pros and cons to any partnering strategy. here we have a few really strong reasons why this is a critical part of our strategy. First and foremost, it takes 7 to 10 years to develop a biosimilar internally. You can imagine that of the 24 assets we have defined, that means that anything we haven't covered in market becomes a licensing opportunity. Sandoz is positioned as a very attractive partner, because you've heard from my colleagues about the commercial performance and scale that we have. When we pursue licensing opportunities, clearly the deal framework is well evaluated, looking at financial threshold, fair value return for shareholder and external competitiveness.
We feel really strongly about that aspect of our partnering. It's right now at about a third of the pipeline, which allows us to capture opportunities we can't capture otherwise. Where and if allowable, leveraging our balance sheet to expand the pipeline.
I have three questions from Graham Parry from Bank of America. The first one: How does 1/3 of U.S. generics first to file compare with industry in the U.S.? How high can this go, and what is the IRR on development cost for FTE versus day one launch versus late launch? Second one: In terms of being selective, in terms of where choose to develop biosimilars, what factors go into selecting which to develop? If we think of big commercial markets that will go generic biosimilar by early 2030s, are there any you wouldn't go after, and why? For example, IL-17s, IL-23s, GLP-1, PD-L1, for instance, or are these in the business plan?
The last one, probably for Glenn: How much of the 350 basis point margin upside from operational improvements are more readily achievable due to the separation? Could this have been achieved as well as part of Novartis?
I think actually the last question will actually cover quite a lot with Colin. Perhaps we can park that to Colin, considering we've only got a couple of minutes left. Pierre?
Sure. What I can say on the U.S. pipeline is that you'll remember when Keren presented, that she talked a lot about going through a period of restabilizing the business and rebuilding the focused pipeline for the U.S. What I can confirm is that the pipeline that has been rebuilt is more than two-thirds focused on opportunities that meet the criteria of first to file across different categories of that bucket. On internal rate of returns for those kind of projects, our policy is not to comment on individual return rates on either assets or geographies. On a bio selection, as to what biosimilar do we choose or not choose, and why, for targeting for development or licensing, we use a very comprehensive strategic review process.
First and foremost, looking at the lasting power of that, of that agent in the therapy area. For example, when you're looking over a 10-year period, you may assess gene therapy disruption, you may assess new originators coming to disrupt the position of the biologic that you're targeting. We do a very deep assessment using competitive intelligence as well as public, publicly available resources to assess, and we continually monitor at every milestone along our strategic pipeline framework. I wouldn't comment as to which ones we would target and which ones we would not, other than to say that our framework and operating process gives us very good line of sight.
Shall I?
Thank you. Just one more question from Balaji Prasad at Barclays. Maybe this is for Pierre. Can you comment on the future, next five to seven years of biosimilar competition? Do you anticipate newer entrants into the biosimilar market in Europe or U.S., or will it be largely incumbent company? Thank you.
Great question. Actually, I can comment on that because most of the assets coming within the next five years are actually, have clinical trial activity, or publicly identifiable, competitors, in the arena. Typically, we see an entrance of between five and seven competitors in each primary competitive field. It could be larger, so there are typically 10- 12 companies developing, but we think in the higher-regulated markets with very high threshold for success, particularly in the U.S. and in Europe, we would see five-seven competitors, and most of those are quite similar to some of the familiar names that you see today, with a few, exceptional new entrants.
Thank you. I think we're at time, so thank you very much for the three of you. Thank you. Now I'd like to move on to the financial outlook and the compelling sustainability story. Before I talk about the sustainability story, I'd like to invite Colin to come to the stage. Colin has been our CFO for just over a year. Previously, he was CFO for Vifor and Evotec SE. He's a board member of Siegfried AG and has deep capital markets experience, particularly in terms of the Swiss stock market. Colin, the floor is yours.
Thank you, Richard. As Richard said, I joined Sandoz from Vifor Pharma, and I think what is relevant that in 2017, I led the separation of Vifor from Galenica onto the Swiss Exchange, and I feel very privileged to be here doing something similar with Sandoz. You've heard from Gilbert, Richard, and my colleagues throughout the course of the day about the uniqueness and exciting potential of Sandoz, and it's my job now to summarize that from a financial perspective and what it all means. The best way to do that is to look at three distinct time periods. Firstly, the past, 2021 and 2022, where there was a challenging economic environment. Secondly, the present, 2023, which is a year like no other, when we're separating the company to be standalone.
Most excitingly, the future, the period from 2024-2028, when we will exploit our potential as a pure-play generics company. Looking at the first of these periods, 2021-2022, we all know the economic events and macro developments that dominated this period, the pandemic, the war in Ukraine, and subsequent supply-side inflation. I think what was really impressive was how strongly the business recovered coming out of COVID, and we continued to invest in the pipeline and commercial initiatives throughout the period. My next slide is a summary of the key financial highlights for 2021 and 2022, and starting with net sales. On a constant currency basis, they grew strongly by 4% in 2022 versus 2021.
Core EBITDA margin declined by 0.9%. This was due to inflation, which occurred in the second half of 2022, and that is a known industry-wide issue. Thirdly, free cash flow as a percentage of net sales declined slightly. This was due to a positive reason. We needed to build up inventory in support of the strong top-line growth. Looking at the net sales development between 2021 and 2022, we will report in US dollars. Restating the 2021 sales for 2022 currency rates, we grew 4% in 2022 on a constant currency basis. This growth was driven by strong volume, which was approximately 10% or contributed $0.9 billion to the top line. This was offset by price erosion of approximately 6% or $0.6 billion.
It's important to highlight that price erosion is a part of the generics business, and that 6% erosion is absolutely consistent with what's occurred in previous years. This slide, Richard presented this morning, but it's significant, and I'd like to cover it again. It shows the distribution of our sales between the two businesses. Firstly, generics in 2022 was 79% of the total business, and what's key from a financial perspective is that generics is diversified, stable, and a cash-generating platform, as Richard highlighted this morning. Biosimilars, which currently account for 21% of our business, grew very strongly, 9%, which is absolutely consistent with where we want to go with the pipeline of 24 assets that Pierre just described. Looking at the distribution of our net sales in 2022 by region, Richard covered this slide this morning.
Really importantly, our European champion, which accounts for 50% of our total sales, grew by 6%. International, despite the challenges in Ukraine and Russia, grew 7%. As Keren described, after many years of significant decline, the US business stabilized in 2022 ahead of the key biosimilar launches that my colleagues have described. Looking at the EBITDA bridge between 2021 and 2022, there's three bridging items that I'd like to highlight. The first one is the operational improvements, which contributed 80 basis points. That came from procurement savings and conversion cost reductions. That really is a proof point for the margin expansion that Glenn spoke about in his session. Secondly, investments.
These had a negative impact, but they were related to positive business developments. There were two factors: firstly, investing in commercial initiatives that drove the strong top line, and secondly, the integration costs related to the two acquisitions, the Aspen business in Japan and GSK cephalosporins that Paco talked about during his session. Thirdly, inflation occurred in the second half of the year, and that caused that 120 basis points decline in the margin. As I said, that's a known issue and an industry-wide challenge. The second of the time periods, the present, 2023, as I said, it's a year like no other. We're separating the business. What's really exciting is the two bio launches timed in the second half of the year.
We will continue to invest in capability, capacity, and pipeline. We have some investments to make to operate as a standalone company. Looking at the quarter one, which we published, we continued the strong momentum. Richard spoke about the six quarters of continuous growth. We recorded an 8% growth in the quarter. What was really encouraging was to see a 16% growth in Europe, our champion, and also a 17% growth in biosimilars, which is the core of our strategy going forward. Looking at the EBITDA bridge, there will be a decrease in the EBITDA in 2023 versus 2022. We will decline from 21.2 to between 18%-19%. Two very clear reasons for this.
Firstly, the cost to operate as a standalone company will have an impact of approximately 100 basis points, and then inflation on the supply side will be up to 10%. What's really encouraging is that we start to see significant signs of that inflation modifying, which is really encouraging as we go into 2024. Most excitingly, looking at the future, this period of 2024-2028, when we will operate as a standalone generics company. What we're committing to is mid-single-digit growth. That will be driven by what you've heard from my colleagues, the 400 assets in the generics pipeline and the 4 biosimilars launches. We will have a core EBITDA expansion to reach 24%-26%, and you've heard from Glenn about the operational improvements that will drive that.
In addition, we will have the volume impact of leveraging a bigger business over the infrastructure, a mix shift, and also operational efficiencies from managing the business differently. Cash is fundamental, and I would just like to use this slide to highlight what's going to drive our cash over the midterm. You've heard from my colleagues throughout the course of the day that we're in a super attractive market. We have scale and a leadership position and multiple levers of top-line growth. Secondly, our margin will expand. You've heard of the drivers of margin expansion, the mid-single-digit volume growth, the mix shift, the operational improvements that Glenn described, and organizational efficiencies, and those two together will drive free cash flow. On top, we will make better use of our working capital as we operate as a standalone company.
Looking at the top-line development over the period from 2023- 2028, we're committing to a mid-single-digit growth. This will be balanced across both businesses. Firstly, with generics, given the scale, we will grow that part of the business, then most excitingly, on biosimilars, with the 4 launches, we will shift the proportion of our sales in biosimilars from 20%-30% over the period. That will have a positive impact on our margin. Looking at the distribution of the growth by region, 50% of the overall growth will come from the U.S.. That shouldn't be a surprise, given the 4 biosimilar launches. The other 50% will be equally distributed between the European and international regions. This slide is really key.
It's the margin expansion, the quality of our business, and I'm going to spend a little bit of time on it. We're committing to go from 18%-19% in 2023, to 24%-26% by 2028. It will be driven by 4 things. Firstly, volume and price. Let's assume 5% growth a year, mid-single digit. That will generate approximately 30% additional volume, of which we can then leverage over the existing infrastructure. Secondly, product mix. I highlighted that the proportion of bio sales will increase from 20%-30%. Historically, the gross margin on biosimilars has been roughly 20% higher, and that will then lead to a 100 basis points improvement in the EBITDA margin. Operational improvements, you heard from Glenn, will contribute 350 basis points, approximately 60% of that coming from procurement.
Organizational efficiency will deliver 150 basis points, and that will be through automatization, standardization, and redesigning the organization. The obvious question is: How is that margin expansion phased over the period between 2023 and 2028? I'm happy to go through each of the four components here. Let's start with volume. We think that will be broadly linear over the time period, that margin improvement coming from volume. Similarly, product mix, we think, will be more or less equally phased over this period. Operational improvements, we think procurement will be more skewed towards the front end, and the other three components of operational improvement, network design, vertical integration, and operational excellence will be more skewed towards the second half of the time period.
Organizational efficiency, we see as being more towards the front end of the time period, skewed more towards the front end. Hopefully that gives you some color for the modeling that I know you now need to undertake. Looking at our CapEx investment over the period, when you look back over the past, we've spent approximately 2% of sales annually on replacement CapEx, and we expect to continue at that rate going forward. That results in $1.1 billion of CapEx on replacement over the time period. Secondly, the bottom left-hand corner in the pie chart, generics expansion with a 30% growth in our volumes. We will spend $0.6 billion in support of that expansion. Then the top left-hand part of the pie chart, the biosimilars investment, $0.6 billion.
You've heard from Richard and Glenn that the majority of that is in support of the Slovenia Lendava biosimilars capacity investment. Looking at cash flow generation, Richard covered this during the morning session. We expect cash flow to increase by more than 2.5x between 2022 and 2028. Clearly that is coming from the top-line growth, 5% per annum, mid-single digit. The margin expansion from 18%-19%, up to 24%-26%, and a more efficient use of our working capital. We currently invest about 35% of our sales in working capital to support that. We think there's an opportunity to significantly improve that. In the short to midterm, the period 2024, 2025, we do have some investments to make.
First of all, in the bio capacity, $0.6 billion that I spoke about previously, and one-time separation costs of $0.7 billion. Richard covered our balance sheet and capital structure this morning, it's critical, I'm gonna highlight and go through it once more. At the separation, we will finance the company through bank debts. We will access the capital markets in the months following the separation and refinance the company. What we're anticipating at the separation, the net debt to core EBITDA ratio will be in the range of 2-2.5. We're targeting an investment grade, we're in the process of securing two investment grade ratings.
We think that with this strong balance sheet and the investment grade ratings, we're gonna be clearly differentiated from our competitors and in an extremely strong position to do inorganic deals going forward. Capital allocation is my next slide, and Richard spoke about this during the morning session. Capacity expansion is our first priority, to invest in the organic business, and I've spoken about the $0.6 billion for generics growth, and the $0.6 billion in the biosimilars capacity and capability. Standalone capabilities, the $0.7 billion that we need to invest to operate on a standalone basis. D&R is currently in the range of 9% of sales. We're gonna keep it at that level and shift the proportion of the spend more from generics into bio during the plan period.
The second priority for our capital will be to return the capital to shareholders, we're gonna do that through a progressive dividend policy, I'll come to the details of that in a moment. Thirdly, as Richard explained this morning, when the right opportunities present themselves going forward, you know, we will be able to leverage our strong balance sheet to execute on those possibilities. The guidance is my closing slide, Richard presented this during the morning session. It's critical. Starting with the top line, we're committing to mid-single digit for 2023 and mid-single digit in the midterm to 2028. On core EBITDA, I've explained very clearly how we're gonna expand the margin from 18%-19% in 2023 to 24%-26% by 2028.
Dividend policy is a percentage of core net income, 20%-30% in 2023, expanding to 30%-40% by 2028. And as Richard also highlighted this morning, we will pay a full year dividend for 2023, even though we will only separate in the second half of 2023. EBITDA, top-line growth, EBITDA will really drive the margin expansion, the bottom line performance, and on top of that, we will increase the payout, and that will lead to a very healthy expansion of the dividend. With that, I'd like to hand back to Richard.
Thank you, Colin. Okay, I'd just like to now spend a little bit of time reflecting on our compelling sustainability story. As I started the presentation this morning, clearly, you know, we have a very strong sustainability story. Access, clearly, is much of the focus of our business. It's really our purpose for existing and our core focus in terms of how we want to drive the business, particularly around how we democratize biologics, how we bring biologics to patients, couldn't hope to aspire to have those in many markets around the world. Clearly, as we step away from Novartis, we have a strong environmental framework which we can build on, and again, we'll communicate specifically in terms of what those objectives and goals will be in the early part of quarter one next year.
As an organization, we will continue to champion our people to drive diversity, equity, and inclusion. As Gilbert started this morning, you know, we have an incredible board and a great organizational setup as we come out of Novartis in terms of our compliance and our risk management and our overall corporate governance. Of all of the slides today, this is the one that I'm most proud of, because this is really what Sandoz is about. It's about driving access for our patients around the world. You know, significant healthcare savings, $17 billion direct savings just to the U.S. and Europe, nearly $200 billion of savings in terms of our social impact every year, and reaching over 500 million patients every year for the products we manufacture and serve.
As we've brought and become a leading player in the biologics market, we've opened up markets. We have 90 markets where we've launched biosimilars. Many of those, the first time those products have been available in the market. We have 8 biosimilars currently marketed and an unrivaled pipeline of 24 assets, which allows us to continue that journey and offer transformational medications to patients. We have a huge pedigree around antibiotics. We have over 50 different molecule antibiotics. That's one of the broadest and deepest pipelines in the industry. We're the only remaining vertically vertical manufacturer left in the Western world. That gives us leverage to government, to patients, and a responsibility in terms of how we support that. We educate over 40,000 physicians a year, and we continue to invest in this critical medicine going forward.
This allows us to have very strong engagement with our stakeholders. I, as Gilbert said, I'm the chairman of the IGBA CEO Advisory Committee. Rebecca is Vice President for Medicines for Europe, and Keren is also Vice President for AAM, again, the Affordable Medicines Group in the U.S. This gives us a very strong voice with government, with payer frameworks, and across the industry. As a company, also, we pioneer Act4Biosimilars, helping payers, physicians, and patients understand the opportunities that biosimilars can bring, opening up markets and really driving change. As a manufacturer, we engage heavily with all of the regulatory authorities, whether the FDA, the EMA. We're investing in technology platforms to support the AMR, antibiotic resistance, agenda.
As a manufacturer, we're part of the AMR Industry Alliance, which really looks at green manufacturing, wastewater management, et cetera, particularly in the antibiotic space. We've come a long way in terms of our environmental responsibility as part of Novartis. We've significantly reduced our greenhouse gas emissions by 49%, our water consumption by 42%, and our total waste by nearly 60%. As we think about these areas going forward, clearly, we'll consider our programs around decarbonization, our waste and water management, and our sustainable supply chain. As I said, we'll provide guidance on these in quarter one next year. With the 22,000 associates we have in our organization, we will continue to champion diversity, equity, and inclusion. We have a very diverse workforce with 47% women in representation in management.
We have engagement and a connection to our purpose as we attract and retain our talent, and we're continually retaining and upskilling our talent. When you look at our Glassdoor scores and our own industry internal metrics, we are certainly ahead of the industry significantly and a leader in our sector. We're committing, going forward, to transparency and pay equity, with 100% of associates covered by pay equity studies by 2025. We want to maintain our strong gender balance throughout the whole organization and continue building an inclusive and open and collaborative organization through its leadership and its talents. All at the same time, building on our very strong governance framework. Clearly, you know, a world-class board led by Gilbert, fully independent board members with 40% female representation.
A high, strong corporate governance inbuilt in our organization with a strong culture of doing what's right. Clear and robust code of ethics, an integrated risk management platform that we will inherit and take from Novartis. We will continue to commit to best practice reporting, and as I said, we will give guidance, the Q1 2024, when we publish our annual report in terms of GRI and TCFD, and other rating agencies. I guess, just in conclusion, you've heard a lot of from my colleagues today, a lot about the business, and thank you for your questions. Just in summary, this is proposed subject to board approval and subject to the shareholder vote, a 100% spin-off, separating Novartis and Sandoz. There will be two completely independent companies.
We propose to list on the Swiss Stock Exchange, our headquarters will remain in Basel, in Switzerland. As Colin has said, we will target to maintain an investment-grade credit rating that differentiates us from our competitors, but also allows us to invest for our future and for our growth. We will publish our second half-year results in line with Novartis on the 18th of July, and we're on track for the second half of 2023 for the execution of the spin. We covered a lot of things today, and these six areas really focus about our match attractive market fundamentals, our leadership and scale, our multiple growth drivers and margin improvement, strong cash flow, and our compelling sustainability story. Perhaps, in summary, I'd ask you to think about four things. First question, really, has our U.S. business stabilized and primed for growth?
I think Keren has done a phenomenal job building a business that now is at scale, and with a pipeline that we see in front of us, can position us and accelerate our growth as an organization going forward. Can we continue our broad growth journey? Again, you know, we are a champion in Europe, very strong performance in international, and coupled with the stabilized U.S., we're confident to deliver at least mid-single digit growth over the planning period. Can we expand our margin from high teens to mid-twenties over the planning period? Again, Glenn and Colin, we see significant opportunities to simplify our network, change our portfolio mix, and drive execution to expand our margin, to return capital back to our shareholders, and to allow us to invest in our organization. Lastly, are we a biologics business?
At heart, 20% of our business today is from biosimilars. We have an unrivaled pipeline of 24 assets and a leadership position with eight assets already launched. We're extremely confident about the opportunities that we can present will not only drive growth, but help drive and expand our margin. Thank you so much for your time today. Ladies and gentlemen, I present you Sandoz. Final Q&A.
Thank you, it's Mark Purcell, Morgan Stanley. Just two. First one on the competitive environment. Samsung Biologics and Pfizer announced today a partnership, a $411 million contract for Samsung to manufacture biosimilars for Pfizer. Given the unprecedented number of second wave of biosimilars coming up towards the end of the decade, do you expect the competitive environment to increase as people see the same attractive opportunities you've described? Secondly, obviously, some parts of the business, when it comes to IP, pricing, et cetera, there's risk, and there's also a lack of visibility. It'd be great for you to help us understand, on the IP side of things, how we should think about that in terms of where we have certainty of launch.
I guess, the Enbrel situation is one end of the spectrum, Humira in the middle, and others, you've been successful. How should we think about the timing and IP? Also operationally, how do you run scenarios around that? Whether there's a, an on-time launch, a 2-year delay, a 4-year delay, how do you sort of manage the operation in the business? The secondly is just around pricing. If the environment were to become more competitive or the originators were to become a lot more aggressive in terms of cutting their price, how should we think about the impact on your business, I guess, across the column on margins, et cetera? More detail there would be helpful, too.
Fine. Perhaps if I take pricing first, then I'll ask Pierre to comment on the first two questions. I understand your logic, but I think let's take a step back. You know, there's today, as I said, five players account for 80% of the market already. It's already consolidated. You know, pricing is always a factor, but, you know, we've not launched a biosimilar in Europe for three years. Yet the business is growing at 16% in cash terms, three years after that launch, at a very healthy margin. So even with a you know, high degree of competition, the margin expansion and the opportunity is still quite significant. So I don't think you're gonna get the same level of commercial intensity that you would, say, in a, in a small molecule environment, which.
Because I think the dynamics are very different. If you look at the pipeline going forward, you know, if you look at the four launches we've got, you know, probably maybe two, certainly one of those, we'll see no competition for quite a period of time. Others, there's a lot of competition, but we're a generic drug company at the end of the day. We're used to competition, and we're used to leveraging and creating value. I think particularly in Region Europe, even when we weren't first to market, we end up as a leader in the market because of the commercial scale. You know, I can understand the logic, but I just don't see it evolving in that way because the capital needed, the complexity.
Also, then the breadth of the portfolio means that, you know, there'll be some assets that clearly many players, so like, you know, ADA, but there'll be other assets with much lower levels of competitive intensity. Then I think if you look at things like HC, the human growth hormone, 15 years later, we're still at number one, and it's still attractive. It's that fundamental that, to me, makes this sector so exciting. Pierre, do you wanna perhaps add some comment? Get you a microphone.
Thank you. As to the question, I think, was Pfizer-related in their announcement about an hour ago, related to their partnership with Samsung. I did see that as well in my email. Thank you. I think I would refer to their public comments that they previously made from a capital allocation and development strategy. Pfizer has clearly made a statement in the last 18 months that they actually plan to lower or limit their investment only opportunities completely in our similar space. Until we learn further information, I would read today's announcement as a transfer of their in-market portfolio into a consolidated third-party player, to be determined once more information plays out. I think the larger question was: Where is the industry going in terms of competitiveness and entries?
There, we continue to always have line of sight on the next five- seven years because of clinical trial activity. We continue to see most markets with five-seven primary entries of high quality, high likelihood companies that will enter a time of LOE. Over the long term, as Richard said, there are very high technical barriers to entry, in addition to financial barriers on development costs, and lastly, capital investment barriers in terms of the ability to invest in internal manufacturing. I think the space will continue to be a very difficult and high barrier to entry. The second question was on IP visibility and timing related to some of the assets.
I'll reference here that clearly at adalimumab, we have a U.S. settlement and are entering the market in early July as part of that wave and settlement. On natalizumab and denosumab, we're in active litigation on both those assets, and as a matter of policy and good practice, we don't comment in areas of active litigation other than to say that we're very confident in our position. We look forward to resolving it as soon as possible, and ultimately bringing the product to market as quickly as possible. Lastly, where we aren't engaged in litigation, there is active industry litigation with aflibercept. One of the first filers on that brand is in active litigation.
We monitor the litigation, and we'll keep you posted when appropriate on the outcomes of those, with one of the key outcomes expected to be a trial decision in the latter half of this year, related to one of the patent families related to aflibercept. Ultimately, the thing to remember as well, is that whenever we create a biosimilar pipeline, as Claire laid out, we create one global pipeline, and we scale it. Natalizumab will be launched in Europe, and there we have a very high confidence and conviction level on our ability to launch in the latter half of this year, as will other products. I would remind you of that as well, because it's part of our balanced distribution of risk and opportunity.
I've got two very boring financial ones, I'm afraid. First of all, tax. There was no mention at all about the tax rate and tax structure. Any thought? I mean, I guess you've obviously been spun off, but is there any change at all in tax that we should consider versus the parent, when we think of Sandoz, an independent entity? Secondly, just on the debt. You spinning off, you say then you're gonna refinance in the capital markets. Is there any plan to pay down the debt? I mean, are you quite comfortable with 2-2.5x leverage, sort of longer term, as a capital structure for the company?
If not, I mean, where do you see as a sort of sustainable long-term level of debt, given your ambitions to also have some flexibility?
Yeah. Tax, we expect to be very stable over the plan period at about 22%-23%. In terms of the capital structure, given the strong top-line growth, the mid-single-digit top-line growth, plus the margin expansion and the cash generation, we think that, of course, there's gonna be a decrease in the overall net debt as a ratio of EBITDA. The way that we will structure the refinancing of the company is with a range of maturities over the midterm.
I have three more from Balaji at Barclays. First one for potentially Gilbert, if you'd like to comment, or Richard. What are your thoughts around the significant gap between the social value that the generic sector provides and the equity value it gets, which is driving a flight from future generics and biosimilars investment, as you've seen some of your peers do? The first question. Related to the last one that Colin got also, can you please discuss the landscape for M&A and BD in North America and Europe? What kind of deals would you be inclined to look at, and the size of the deals that you're comfortable with in conjunction with this, what kind of leverage would you be comfortable for the company versus the leverage at the time of the spin, which you might have already addressed?
Lastly, in the EBITDA margin progression chart, which is rather compelling, I was curious to see that there are no headwinds to margin expansion. Is there anything that could pose possible headwinds to margins, even if the overall direction is still positive and in line with your guidance?
Okay, Gilbert, do you want to go first, or do you want me to take it?
Look, it's a great question. I'll perhaps comment first and then make sure. Look, generics, I think, clearly, there's a positive and negative side of the story. Generics are very much, to me, part of the solution in terms of global healthcare. In the U.S., 90% of the volume is generic healthcare, at probably about 10% of the cost. I'll give you some numbers for the U.S. that perhaps explains the problem. Our sales in the U.S., if gross, are over $10 billion. Somebody else is making, you know, $8.5 billion out of that money, then it's not us. The payer framework and the systems are what's driving a lot of this challenge.
I think a lot of the issues that you kinda currently see today on things like oncology, is that the margins are squeezed as a supplier, but your ability to see a fair return for that price is incredibly difficult because unfortunately, the middle actors in this have a significant amount of buying power, and even when you can be sole supplier, you can be selling underwater because of the portfolio effect and the leverage that they have.
I think that's now starting to be recognized by governments and payers. I think it's less extreme in Europe, to be brutally honest, we're having very concrete conversations with governments and payers, particularly around things like anti-infectives, that, you know, on one hand, they want a sustainable supply chain, yet we need to invest significant amounts of money to do that. Actually, I'm encouraged by the dialogue. I'm actually encouraged by the signs we're starting to see in the U.S. It does, you know, it goes back to, you know, why should we be selling a product to treat cancer for the same price as a pack of M&M's? Quite honestly, it's terrible. I think it's a significant opportunity to drive that. We have the scale, we have the relationships to continue to talk and move that forward.
Okay, thank you.
Your second question, M&A deals. I think we said right at the beginning, look, I think we have a plan here that doesn't require M&A or BD, certainly of a transformational nature, to deliver the plan over the planning period. We do about $100 million a year, plus or minus, of sales from BD and M&A, small product deals, transactions, and that's always been in the business. We've assumed that level going forward. Clearly, I think over the midterm, once the free cash increases, that would open up the optionality. Do I see assets? I think the U.S., as we've seen firsthand, it's a difficult environment to transact with the FTC. I'm probably more interested in technology platforms or possible assets for the U.S..
Similarly, for Europe, given our scale, there's no obvious company that you would ever really consider acquiring. Again, it's more portfolios or technologies. International, difficult to execute, but I think again, there, we clearly we've acquired mature brands or we've found assets. Again, it's probably more likely around the assets class rather than obviously in terms of companies. That's very much more for the medium term. I think the short term, focus on our execution, focus on driving efficiencies in the business, stabilizing the business post the spin, and delivering on our agenda.
To the margin expansion, clearly, we're at the start of a journey now, and we're committing to 24%-26% in the midterm. When I go through the checklist of the different components driving that, what we've assumed in our model is that price decreases will be consistent with what we've experienced in the past. From 2024, 2025 onwards, we assume that inflation goes back to low single digit levels, that's consistent with what we've experienced historically. On the volume, improvement in the margin with our 400 generics pipeline, plus the four biosimilar launches, we feel confident about that. Again, on the mix shift, given the four launches, we're confident on that. On the operational improvements, the 350 basis points, given all the initiatives that are in Glenn shop, we feel confident about that.
The organizational efficiencies, given that we have a 30% increase in the volume, and we can leverage the infrastructure and work fundamentally differently, we feel good about that. Now, the midterm is quite a long period, and of course, things happen, but the responsibility of management is to react to that and deal with situations as they present themselves. Based on what we currently know and can currently see, compelling is a good word. The margin expansion looks compelling.
Thank you.
Just a very quick one. Katarina from JP Morgan. Just to follow up on your comment on inflation. If inflation were to stay elevated or accelerate, how big of a headwind would that be? I guess, put another way, like, how much of inflationary pressures can you pass on from a pricing perspective versus how much of it do you have to absorb?
Clearly, we work continuously with regulators and healthcare providers to try and get a fair and sustainable pricing for the benefit that our medicines bring. Clearly, there's a lag between input cost inflation and getting that pricing, and it's a continual work in progress. As I said, in 2023, our expectation is that inflation could be up to 10%. What's been really encouraging in the first six months of the year, we see significant signs of inflation decreasing, particularly in areas such as utilities, and we do expect a normalization. You know, just as the ECB and the Fed are expecting a reduction in interest rates, we see that in our inflation expectations as well as the supply chain normalizes.
It's not a Sandoz specific, it's an industry drive. But certainly, you know, we have seen payers now having a conversation. I think they see the nature of the supply chain. You know, certainly in a couple of markets in Europe now, we've found mechanisms to either get coverage for inventory, to better secure supply as a way of compensating for inflation with payers. I think we're having the dialogue. It's not easy to take price, but certainly we've seen and there are examples in the U.S., where Keren and the team have equally been able to do that as well.
I have more questions from Graham Parry from Bank of America. They're all for Colin. U.S. business was down 2% in 2022 and Q1 2023. What growth is assumed in the US generics business in the business plan guidance? Is this essentially a loss leader for biosimilars? Second one on depreciation and CapEx. Depreciation cost was $200 million in 2022, CapEx program, $2.3 billion. What is the utilization rate depreciation years on PPE? Is it fair to assume depreciation costs of $400 million in 2028 to help reconcile with core operating income margin being reported by Novartis and forecast by the street now? Maybe you also want to address the one that we asked in the previous session on 350 margin, right?
How much would come if you would stay with Novartis?
Could you say that last part again?
The last one was the one from the previous. How much of the 350 basis point margin upside from operational improvements are more readily achievable due to the separation? Would these have been achieved as part of Novartis?
Well, let's start with that one. I think what's really interesting as a standalone generics company, the cost of sales becomes 50% of our net sales. It gets an incredible amount of focus in a generic company versus being an originator. That's because we continually get asked the question: without the scale of Novartis, will you be able to get better input costs? We think absolutely. You've heard all the things Glenn talked about, which is leveraging the scale, the 30% volume growth, about reducing complexity with a number of suppliers, and focusing the purchasing and procurement organization. I think the second question in reverse order that Graham had, was around depreciation and CapEx spending.
We do in the appendix, this capital markets day deck, have a bridge between operating income and EBITDA. What you see in there is that our depreciation in 2022 and 2021 was about $200 million, which is absolutely consistent with the replacement CapEx that I was indicating in the presentation, that we spend 2% of our revenues, which of course, were approximately $10 billion. We spend about $200 million a year on replacement CapEx, and our depreciation is currently $200 million. Obviously, with the investment in capacity, expansion, and bio-capability, we will have a increase in the fixed assets on our balance sheet, which will inevitably lead to an increase in depreciation in the midterm.
I think your point there about the U.S. growth, I mean, I think, you know, we went through a phase post-Aurobindo, where clearly in a lot of third-party deals that pushed out, which dragged the business down. I think ±2% is, you know, really showing that this business has stabilized. Do I see the biologic? Absolutely not. Though, you know, these are very valuable, and the originator prices, even with significantly steep discounting, these are highly attractive opportunities, so they're highly accretive. They're also accretive because then, you know, once you have the infrastructure and the relationship with the payers, adding more and more assets into that mix, means that you can extract more and more value. So as the sales drive, the top line comes more and more flow through to the bottom line.
I think to the third part about were the synergies with Novartis, could we extract them without the separation? I guess, actually, a lot of it is quite difficult. If you look at things like IT platforms, systems and processes, you know, we're a division of a global organization at the moment. That, you know, just doesn't operate like that. I think the opportunity for us is ultimately to have the right systems and processes for a generics business, and not the systems and processes for a global pharma organization. In theory, I understand the question, but I think the reality, and it's been possible to execute if we stayed within Novartis. Okay, if there's no more questions, thank you so much for your time today. Thank you for your questions and engagement.
I appreciate the challenges of travel with the slightly bizarre weather. I blame the Canadians for that one. Thank you all, safe travels home, good evening. Thank you.