Good morning to those joining from the U.K., Central Europe, and the U.S., and good afternoon to those listening in Asia. Welcome, ladies and gentlemen, to AstraZeneca's Investor Day 2024 webinar for investors and analysts. Before I hand over to AstraZeneca, I'd like to read the safe harbor statement. The company intends to utilize the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements with respect to the operations and financial performance of AstraZeneca. Although we believe our expectations are based on reasonable assumptions, by their very nature, forward-looking statements involve risks and uncertainties and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these forward-looking statements.
Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements. Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation and webinar. There will be an opportunity to ask questions after today's presentations. Please use the Raise a Hand feature to indicate you wish to ask a question, and remember to unmute your line when invited to speak. With that, we'll now connect you to the auditorium in Cambridge.
Welcome to AstraZeneca in 2030. A pioneer in science, our unrivaled expertise across a range of modalities is revolutionizing patient outcomes. In oncology, our best-in-class medicines are increasing survival outcomes across a range of tumor types, with cure becoming a distinct possibility in many settings. In biopharma, we're transforming healthcare for people living with chronic diseases and delivering long-lasting immunity, so billions can live healthier lives. And in rare diseases, we're leveraging our leadership position to bring treatment options to more patients than ever before. Through our strength across our regions, supported by our intelligent, sustainable supply chains, we're putting our medicines into the hands of patients faster than ever before, leaving us poised to deliver many more years of industry-leading growth.
As we've grown our company, we've remained agile, harnessing the power of science and innovation and our global reach to make a positive impact on people, society, and the planet. We will unlock our potential and deliver industry-leading growth to 2030 and beyond.
Morning, everybody. I hope you had a good night last night and enjoyed the dinner for those of you who were with us. And those who had a chance to look at the DISC this morning, I hope you enjoyed the visit and understood why we are so excited to be here and why our scientists are so pleased to be here. Today is a very special day for us because it's the starting point of a new journey of growth to 2030 and beyond. And it's really a great pleasure to present to you our strategy over the next few hours, our ambition, and how we actually plan to get to this new goal we've given ourselves for 2030.
And it's really a great pleasure to do it here from this site, which has been a little bit long coming, but I'm sure you've realized is a, an amazing place for people to do science. It's been an amazing place for us to bring the company together over the years. The MedImmune organization and AstraZeneca, we tend to forget that's where we started from 10 years ago. It's brought everybody together here. It's really galvanized our scientists to develop, build the best lives in the world. That's the mission we gave them 10 years ago when we started on this site. And today it is really something that will fuel our pipeline and help us deliver the very ambitious goals we've given ourselves. Some of you may have seen this picture outside and the, and the name José Baselga.
José is with us every day. He was a giant of cancer care. He was a fantastic scientist, a fantastic clinician, a great doctor, a great leader, and a very good man, and he had a huge impact on this company in a very short period of time. And some of the work actually that will be presented today was triggered, was initiated by José when he was head of R&D oncology, and we decided to actually recognize him outside of this room. So these are the forward-looking statements. You know them, they are very traditional.
I wanted to start here because 10 years ago, a bit more than 10 years ago, actually, we told you that we would achieve $45 billion by 2023, which at the time was $45 billion, but actually using 2023 exchange rates, would have been more like $40 or $42 billion. So it was a very ambitious target, and it really was a fantastic rallying cry at the time for the company to mobilize and work toward this very ambitious goal... and actually we delivered it. It was certainly very challenging because you can see that we went through a period of time that was a little bit scary, I have to say. We declined, but we managed to turn the company around, and we did this through science.
We did this through focusing on great science, great products, rebuilding our pipeline, and launching the medicines that today are blockbusters and driving our growth. We did this through a strategy that really hasn't changed overall, but has been very dynamic in the sense of being adjusted as we went along. We decided that we want to focus on science and innovation, growth in therapy, area leadership, having a global footprint, and being a sustainable organization. But of course, as the world changed around us, new technologies emerged, new products, new ways to treat patients. We adjusted to this and complemented our plans with new technologies, and we'll talk about this in a minute as it relates to science. We leveraged our global R&D network. We've constantly focused on building therapy area leadership.
We believe it's important to be a leader, in the areas where you play because you need to be an expert. You need to be an expert in science, but it's not enough. You need to be an expert in how you develop, clinically develop your product, and you need to be an expert in how you commercialize your product. The world of medicine is becoming extremely complicated. We have to become leaders and experts in the field where we operate. We've focused on building this area leadership in oncology, in cardiovascular disease, respiratory disease, rare diseases, and now we are making some progress in, immunology. We've also always focused on growth. Growth is really what drives people, what energizes people, and of course, the best way to create shareholder value in the long term. We've leveraged our global footprint.
We started 10, 12 years ago. I can tell you we were in the emerging market, not that strong. I remember my first visit to Mexico. I left the country almost depressed because we were really in bad shape at the time. Today, we are the number one pharma company in the emerging markets. Leon Wang, who is very competitive, want to be number one in every single country, and in every single country, wants to be number one in every therapy area where we operate. But overall, we are number one in China, and we are number one outside of China and the emerging markets. It's really important because as the world changes around us, these countries actually grow, their economies develop, they become more able to pay for innovative medicines.
They also get older, like everybody, and of course, their healthcare needs increase. And having a global footprint, I believe, is a fantastic advantage in, in terms of globalizing the products we have, including for rare disease. And you'll hear Marc a little later talk about the progress we're making commercializing products that many would think are too expensive for the emerging markets. Actually, we're making very good progress there. And finally, we believe that we need to be a sustainable organization and play our part in reducing carbon footprint in particular, but not only carbon footprint, also reducing the use of natural resources, water, reduce the waste production, and try to the best of our ability, try to get as many patients as possible getting access to our medicines around the world. And so based...
Yes. We have... Yeah, sorry. Yeah, sorry. I was looking at Andy, and I had a hesitation for a second. So we've actually done this, leveraging our R&D network around the world, and we have now five strategic R&D centers. Two in Europe, in Sweden and the UK, here in Cambridge, as you know. Two in the United States, in Gaithersburg, but also now in Cambridge, in Kendall Square. We are actually gonna move into a new facility by 2025, bringing teams from Waltham and elsewhere around Boston to this Kendall Square site. And finally, in Shanghai, we established this large R&D center in Shanghai not long ago. And China is becoming a very fundamental part of our R&D network in many ways.
First of all, of course, developing medicines we bring to patients in China, but that's not the only thing. They are now taking the lead on global programs that are relevant to China and also liaising with local innovation. Innovation in China has exploded, as I'm sure you know, and they're extremely fast and extremely innovative in the new technologies, new medicines they're developing. It's important to actually connect with that new world of innovation and partner with it so we can actually benefit from it, but also help them globalize their medicines. In the last 18 months, 2 years, as you know, we've done quite a number of partnerships and acquisitions in China to leverage this. We also intend to actually leverage our Chinese presence for cell therapy.
Cell therapy in China has a very specific aspect to it, which is in the early phase of clinical development, you can move much faster than anywhere else in the world. And we have the ability through the acquisition of Gracell and the presence of a very strong local AZ, R&D team. We have the ability to leverage that specificity, which is both regulatory driven, but also the way people operate. That will help us save time and be much faster at developing cell therapies. We have, because of our progress with our R&D pipeline, we've been able to upgrade our ambition. Initially, we had the ambition to launch 15 new medicines by 2030, sorry. We've upgraded this ambition to launching 20 NMEs by 2030.
We have already launched six that are listed here, and there's more to come. Certainly, we feel very confident we can deliver 20 new molecular entities by 2030, and on top of it, very innovative products in many different fields. Today, we announced a new ambition, which is to reach $80 billion by 2030. Our ambition is to grow to this level, but also to continue growing beyond 2030, because we want to be a growth company for the long term, until 2030, but also beyond. We want to reconfirm our ambition and our commitment to deliver a mid-thirties operating margin by 2026. We also decided that we wanted to give some indication of our objective post 2026.
As you can understand, and hopefully you will also see, throughout the day, we are in an innovation-driven industry, and innovation means risks. It carries a lot of risks and a lot of uncertainties. It really also brings a lot of rewards if you succeed, of course, and in the last few years, we've tended to be relatively successful. But it carries risk, and therefore, it's very hard to predict precisely what the future will look like. So our commitment, our ambition is actually to maintain our operating margin at the mid-30s, post-2026. But it will, of course, be depending.
Whether it goes above or not, will depend on how much we have in our pipeline, how many products we have to launch, and fundamentally, how much growth we can deliver, beyond 2026, and importantly, beyond 2030. So those are some of the commitments, but also ambition for some of them that we wanted to share with you. How do we achieve this? Last year, we achieved $45 billion, a bit more than $45 billion in sales. And of course, we have to recognize we're going to face headwinds. This is the nature of our industry. We lose patent protection after a while, and of course, a number of governments around the world are trying to address the cost of healthcare and the cost of medicines. So we recognize we'll have to address the IRA impact.
I think it's, and maybe we'll cover this in the discussion, it's important to keep in mind or put the IRA impact in the context of our overall global sales, and it is, we believe, completely manageable. But we also have a loss of exclusivity with Brilinta, Farxiga, Lynparza, and Soliris, and we're working very hard to address those. Soliris, we transfer to, Ultomiris. Lynparza, we're working on the PARP-1, and Farxiga, we're working on combinations, as we will, share with you a little later today. We have an existing portfolio that actually will deliver, ongoing growth between now and 2030. And you know those products, they are listed here, and a lot of them still have a lot of growth, to deliver. And HER2, in particular, and Imfinzi... Airsupra was just launched.
Many of those still have a lot of growth that they can deliver between now and 2030. On top of this, we are going to launch, over the next period of time, quite a number of NMEs. And of course, when we tell you $80 billion, I should have clarified that it's a risk-adjusted number. And if everything worked perfectly, which would be great, but I don't think it's reasonable to expect everything is going to work. But if everything worked perfectly, we would be able to deliver more than that. So the $80 billion is a risk-adjusted number, taking all these medicines that you see as new molecular entities here, taking those into account and risk-adjusting them.
But I can tell you many of them, and hopefully, you'll agree with me, many of them have a very good chance to succeed. The question often is: are they very successful or very successful, depending on how many indications we actually can bring to the market? And beyond 2030, we've been working on those technologies that will, we believe, shape the future of medicine, whether it's in cancer care or in immunology or elsewhere. Antibody drug conjugates, radioconjugates, cell therapy, T-cell engagers, gene therapy for rare diseases, our next-generation antibody bispecifics, products around weight management, obesity, management of risk factors. All of those, we believe, will shape the future of medicine in many fields and will sustain our growth as a company post-2030.
Some of these products will launch, of course, before 2030, but they will deliver a lot of growth post 2030, and we believe will enable us to continue growing through the patent expiries we are facing post 2030. We've listed here a number of our products, the products we believe have a peak year potential, peak year sales potential of $5 billion plus. You can see here, there's quite a number of those that will deliver very strong revenue growth and to 2030 and have very substantial peak year revenue potential.
We also have, not listed here, but we have another bucket of products that you will discover through the presentations today, another bucket of products that have a $3-$5 billion potential, and then a third bucket that have a $1-$3 billion potential. We've created three buckets so you can get a sense for the potential we see in those products, and of course, we can discuss that throughout the day and later as you dig into the presentations more. I've talked about investments in new technologies, and essentially, weight management is, we call it weight management as opposed to obesity, because we believe fundamentally there are two large group of patients.
One is the so-called obese group, who are people who have a very high BMI, or high BMI, or above 28 or 30, and need to probably be treated through titration regimens and combination regimens. There is another very large group of patients who would be well served with a 10% weight reduction, but have risk factors, and you need to manage those risk factors. In this area, we are developing a number of products to treat patients, either with oral medicines that can be combined for ADCs, or injectables, for the segment of patients who need more aggressive weight reduction. We're investing in antibody drug conjugates and radioconjugates, with the ambition to replace traditional chemo and traditional radiotherapy, and you'll hear more about this. We're investing in two...
In particular, two next-generation IO specifics to bring the IO space to the next level beyond PD-1, PD-L1s. We're investing in cell therapy and T-cell engagers with a vision that in cancer, our ambition is to eliminate cancer as a cause of death. We believe the best way to do this for metastatic disease is to attack the cancer with a combination of ADCs and IO, take it to a level where you can actually bring in cell therapy or T-cell engagers, and potentially cure people. Now, the day when we can actually cure people with metastatic disease is not that far away, and if some of those technologies work, it would become actually possible. Finally, gene therapy.
We're investing in gene therapy and gene editing, in particular for our rare disease team and portfolio, and you will hear more from Mark and the team about this. Now, you've seen in the last 18 months or so, you've seen a lot of activity around business development and partnerships that we were announcing. I wanted to bring this slide to you to make sure you understand there was a strategy behind all these technologies. Now, back in 2019-20, we thought we are halfway through our journey, a bit more than halfway, actually, through our journey to 2020-2023. Let's work on our 2025 strategy. We identified a number of technologies we thought we needed to start building.
ADCs, at the time, we had not identified radioconjugates, I have to say. Cell therapy with these T-cell engagers. Gene therapy, no, because we didn't have Alexion at the time, and we complemented gene therapy more recently in the last three years or so. With those technologies, we started building internal efforts, building internal teams and internal programs. We decided to accelerate this over the last 18 months. After really having studied the field and the options available to us, we decided to accelerate the build, and we now have what we believe we need to have in terms of technologies to address those new platforms, those new options, being cell therapy or T-cell engagers, and actually bring them not only to oncology, but also immunology, biopharma, and rare disease in many cases, as you can see here on the slide.
So now the focus of the teams is execution, integration of all these technologies, and we've made very good progress doing this and delivering products, of course, through those efforts. If you look at this, we forecast that those new technologies will actually take a growing proportion of our pipeline in the future. And it's really important, I believe, if you want to be a long-term, successful pharma company, you need to be in those technologies because the world is changing. The industry has been dominated historically by small molecules. 25 years ago, so large molecules, biologics, came to the market with Herceptin and a few others. More recently, in the last 10 years or so, we had IO. And but the world is now changing.
You had, in the past, a product for 15, 17 years to yourself, and then you would lose, lose it to generics, analogs, biosimilars. These technologies will deliver products that will be very difficult to copy rapidly by generic companies. On the other hand, the rate of replacement of products in those coming from this technology is going to accelerate, especially with China coming on board and coming on stream with innovation. And if you look at what is presented at the ASCO, and the number of ADCs is very, very large, of course, and then you have efforts in cell therapy and many other technologies. So the rate of replacement of products will potentially accelerate.
If we are not experts in those technologies in the long run, I think we'll progressively lose, lose ground. You can see here some of the estimates given to the size of the markets in cell therapy or gene therapy. I personally believe that if cell therapy works to the extent we want to make it work, if we can actually bring it to solid tumors, if we can actually turn it into an allogeneic cell therapy approach, the potential is much bigger because you can actually totally change the way many, many diseases are being treated. We also believe we have a unique opportunity with our portfolio, which is, which is quite broad, and it is a strength, we believe. It's a strength because we can combine our products.
If you look at many diseases, the treatment of those diseases is gonna be made of combinations. These are combinations to bring patients to a stable state and keep them in that state a long time, or potentially to cure them... and cure in oncology will require combination. So if you look at oncology, but also cardiovascular disease, our focus is identifying patients early, diagnosing the disease early, intercepting the disease early, and trying to cure patients with combinations. So a lot of our efforts are in identifying disease early, having biomarker to select populations, and then combining. And you'll hear from the team today about our strategy to combine ADCs with IO bispecifics.
If we can do this, we can actually completely change the treatment of many cancers, in particular in lung cancer, first line metastatic. We can actually displace chemo pembro with a combination of ADCs with IO, and transform outcomes as a result. Now, the same approach is true for cardiovascular disease. People who have excess weight have risk factors, and sometimes people think, well, if they lose weight, they're gonna lose the risk factors. The problem is, when people have been overweight for too long, and then, of course, age is also playing a role, they get additional dysregulations, either in their lipid metabolism or in their endothelial vascular walls, and then they stay with their hypertension, or they stay with some level of diabetes because their pancreatic cells are in part gone.
So you have to help those patients manage their weight, but also manage their risk factors. And in that field, we believe with the combination potential that we will show you today, we can actually play a very important role in helping these millions, hundreds of millions of patients around the world, who have some of issue with their weight, but also have risk factors, being heart disease, kidney disease, hypertension, diabetes, dyslipidemia, we can help those people live a longer life. One other aspect of our strategy we wanted to highlight to you is the ability we have to globalize products very rapidly through our global footprint. If you look at the last few years, we have grown a lot in China.
Of course, today, China is going through its own transition from older products to reimbursed products, innovative products, but we've also lost medicines like Pulmicort and a few others that have lost patent protection. China, this year, is starting to grow again, as it launches new products. But outside of China, you can see the very consistent and strong rate of growth we've experienced since 2021, 20%, 40%, 35%. This is becoming a very large part of our company, and moving forward, it will... there's no reason to believe it will not become even bigger. Because we have to all remember, most of the population of the world lives outside of the US, Europe, and Japan, and maybe Australia, Canada. Most of the world lives in these so-called emerging markets.
That's where the population is, that's where the population growth is, that's, of course, where aging is, but also economic development is happening, and therefore, they'll be, they will be able to access our medicines. We've done this, and we will continue to do this, driving our growth, but reducing our impact on the planet. If you look at this graph, the red bar shows you our growth since 2015. And the reason why we use 2015, it's the year when the Paris Agreement was signed, and a large number of countries committed to a reduction in carbon reductions. And since 2015, our company has almost doubled in size, and even though we doubled in size, our carbon emissions are reduced by 68%.
But not only this, our water consumption is reduced by 20%, and we've reduced our waste by 13%. Our goal is to reduce our Scope 1 and 2 emissions by 98% by 2026, and reduce Scope 3, which is, for most companies, the most difficult part, of the, carbon emissions of the entire, supply chain. Scope 3, we will reduce by 50% by 2030, and we're making very good progress in that direction. So we wanted to share this with you because it is important for everybody to remember, it's possible to grow. It's possible to deliver value to patients and shareholders, but at the same time, reduce your impact on the planet. And we are not doing this increasing our cost.
There are cases where, indeed, some of our projects increase cost, but in most cases, what we do reduce our cost. Most of the time, almost immediately, sometimes in the midterm, but it's always economically attractive to do it. I will close by sharing a few thoughts on the catalysts for 2024 and next year. This year, we've already announced 4 to 8 of those catalysts for our positive phase 3 readouts and for our new approval and launches. Out of those phase 3 readouts, actually three will be presented at the ASCO very soon, two of them at the plenary. In fact, maybe we could have even had three at the plenary, but DVO6 readout a little too late.
Still made it into the ASCO, even though the data came out late, which tells you that the clinical benefit must be substantial, otherwise it wouldn't have made it into the ASCO. Also, we have to recognize 2 out of 5 at the plenary is already pretty good. We believe it's probably the first time a company has two presentations at the plenary in one go. So really great data. The point I wanted to make, also in this slide is, on this slide, you have $several billion of 2030 sales. So it really is important because we are not even halfway through 2025, 2024, sorry, and we've already had clinical news approval launches that will generate $billions of additional 2030 sales. It doesn't stop here.
These are the readouts for the rest of the year and for 2025. Many of those you know, and we've only listed here the most important ones. There are more than those, of course. Others are smaller ones, and collectively, these readouts will deliver $20 billion of potential revenue in 2030, non-risk adjusted. So of course, we have to recognize not everything is gonna work, but we think we have a good chance, as many of at, at seeing many of those working out positively, and that will fuel our growth over the next few years. I also wanted to show you this graph because sometimes people... I'm sure some people are saying, "Well, 2030 is so far away. I mean, you know, it doesn't matter.
We'll have to wait so long to know whether you deliver your $80 billion. My message to you is, by the end of 2025, you will always have or already have a very good idea of the trajectory we are on. Not only the trajectory of our sales, having gone through the impact of IRA in 2025, but also what new clinical data we have to drive our growth beyond 2025 into and onto 2030. So within a year and a half, two years, you will have a very good sense for the direction of travel that we are on and whether we have a fair chance to achieve the 2030. So I will stop here and hand over to my good friend, Ruud. Over to you, Ruud.
Thank you so much.
Chronic diseases are on the rise, with 2 billion people having one or more chronic disease. By 2030, one in six people will be over the age of 60, and most of these people will have more than one chronic disease. All of this places unprecedented strain on health systems, but we can change this. In Biopharmaceuticals, we are driving the way to improved outcomes in chronic diseases. In cardiovascular, renal, and metabolic diseases, we're bringing forward novel assets and combinations to address the underlying drivers of interconnected diseases. In respiratory and immunology, we're transforming the care of asthma and COPD with our portfolio of inhaled and biologic medicines, advancing new modalities to treat immune-mediated disease as we aim for remission and potential cure.
In vaccines and immune therapies, we are protecting vulnerable populations from respiratory infections, all so that we can help billions of people live better, healthier lives.
Now, first of all, thank you so much, Pascal, for the introduction, and equally, together with Sharon and the teams of Biopharma, we are extremely pleased to kick off the first of 3 sessions in order to do an in-depth analysis of why we think Biopharma is such an interesting and attractive place to be. You saw it already in the video, but here you see some of the numbers about what is going on in the world, and it's quite daunting to see the enormous impact of chronic diseases across the world. More than 2 billion people in the world are suffering from chronic diseases, whether it is cardiovascular disease, renal disease, respiratory disease, and unfortunately, that will continue in the years to come.
If you see in 2030, one out of six people in the world will have an age over sixty, and we know that those, including myself, by the way, that those people are highly vulnerable in order to develop diseases, and not only one disease, but in many cases, multiple diseases. Equally, the burden on healthcare systems is increasing day in, day out. I have the privilege to travel a lot around the world, and in every country where I am, I hear, let's say, the sense of urgency in order to help health systems in order to manage the enormous patient flow we see across the world. So early detection, early diagnosis are pivotal in order to help health systems and governments in order to further manage the burden on their systems.
The costs associated with chronic diseases are enormous, and that will continue unfortunately, if we are not intervening as an industry, but also as healthcare professionals. So why are we so excited about the journey of Biopharma? First of all, and I want to be humble, but equally, I'm very proud to say that we have a long history and a tremendous heritage in the disease areas we are representing. We have been able, in the last few years, to build the number one cardio renal product is Farxiga, and I know a lot of you have questions about, is there life after Farxiga? And hopefully, at the end of the day, you will say yes, because I have all the confidence that we have a fantastic plan in place in order to help even more patients moving forward.
Equally, we are clearly one of the leaders in respiratory disease, and in asthma, we cover everything from inhaled up to the severe asthmatics with biologics. COPD is one of the... I would say, almost most under-recognized diseases across the world. We see a phenomenal surge of COPD, especially also in the emerging markets, where Pascal was referring to earlier, and clearly, COPD is still the third leading cause of death across the world. Finally, Iskra and Marc Dunoyer will tell you more about what we are doing in order to help the vulnerable patients in the world. Vulnerable for infections like RSV, and hopefully we will launch relatively soon in the next two years, a very attractive new vaccine for hMPV and RSV.
Now, equally, you see, we are building on a very strong platform of existing molecules in AstraZeneca. And personally, I'm very proud that only in the last 12 months, we have launched 3 complete new medicines in the world. Airsupra, for the rescue of asthma, the first rescue medication in the United States. Wainua for ATTR-PN in the first indication, and ATTR is a very important point for attention also during the day. Because we truly believe that we have one of the best, perhaps the best portfolio of treating a very debilitating disease. And together with our colleagues of Alexion, I truly believe that we have an opportunity to really change the curve of this disease.
Last but not least, of course, Beyfortus, together with our partner, Sanofi, where there's a lot of excitement in order to protect the vulnerable babies. Hopefully, you all agree that in the last few years, we have seen a very strong delivery of our commercial presence, and I also would like to take the opportunity to thank all the commercial teams around the world who are working tirelessly to bring our new medicines to the patients who deserve that. But what does it mean, and why do we think that Biopharma is going to contribute to the very clear and bold ambition Pascal was outlining earlier in the discussion, the $80 billion?
First of all, yes, we need to acknowledge that we will face some headwinds, and of course, primarily Farxiga is the biggest headwind in Biopharma in the next few years. But let me also remind you that this is not a falling off a cliff situation. We have full patent protection till October 2028 in Europe. We will lose it in 2026, but our strength in the emerging markets will also help us to keep the brand alive. And we have a very clear ambition that with the fixed-dose combinations, that more than 60 million people will benefit from Farxiga and the combinations in the years to come. Equally, I think we have a very attractive existing portfolio. I've already spoken about Wainua, but clearly also the fact that Fasenra, Tezspire, Beyfortus...
Airsupra are all still having long patent protection. And last but not least, we will focus a lot on the new and exciting new molecular entities in the years to come. Baxdrostat, both in mono and combination therapy, the fixed-dose combinations, of course, and our very attractive NTR33, Tozorakimab. Last but not least, be aware that also Biopharma is completely pleased, obsessed about what is beyond 2030. And I'm sure that Sharon will tell more about our efforts in weight management, our efforts in cell therapy. Cell therapy is no longer the, let's say, the domain for oncology, but is also moving into autoimmune diseases, and we're very, very excited about that story as well. So over to Sharon in order to give us a little bit of flavor of the exciting science in Biopharma.
Thanks so much, Ruud. Can I have the next slide?
Yeah.
As Ruud mentioned, the growing burden of chronic disease, coupled with advances in science and technology, means that we have a tremendous opportunity to create transformative medicines for the tens of millions of people that need them. We can do this because we have invested in capabilities across a broad range of modalities, from small molecules and monoclonals to additional modalities, including antisense oligonucleotides, bispecifics, and cell therapy. What this means is that we can match the right modality to the target or the disease. We are working to catalyze earlier diagnosis and earlier intervention, and this means that we can stop and even reverse disease progression to offer better health outcomes. Now, we know, as Ruud mentioned, in an aging population, that the majority of people are living with multiple comorbidities.
So we are developing novel combinations to be able to address the complexities of disease and the full spectrum of disease. We are moving from treating individual diseases to more holistic healthcare management to offer better treatment outcomes. With the tools and capabilities in our arsenal, we are now able to move from effective management of symptoms to disease modification, clinical remission, and potentially even cure. We can do this because at AstraZeneca, we believe in the power of what science and talented scientists can do. So we are working within our core areas of expertise to explore more innovative, less understood areas of biology, connecting with external experts to expand the boundaries and to be able to identify emerging areas of biology in which we can create more transformative medicines.
This is fueling our innovative pipeline, which in the coming years has an increasing proportion of exciting New Molecular Entities. So collectively, we believe that we have the capabilities to deliver on our bold ambition. If I leave you with one thought from this slide, it is that Biopharma is not following these trends. We are driving these trends and driving towards creating transformative medicines for the tens of millions of people that need them. Turning now to focus on three exciting new areas in which we are building today for long-term impact, let's first explore new modalities which we are leveraging to be able to address a broader range of disease. Starting with amyloidosis in our core focus area, AstraZeneca is uniquely well-positioned to drive competitive differentiation.
Beginning with our TTR silencer, Wainua, which is designed to halt hepatic expression of the proteins that lead to formation of amyloid fibrils, with utility as a monotherapy or in combination with our depleter, ALXN-2220, a monoclonal antibody that is designed to bind, disrupt, and help to remove amyloid plaques. Together with our Alexion colleagues, we are building an industry-leading portfolio in amyloidosis, and we believe that multiple mechanisms of action may be necessary to treat the full spectrum of disease, including severe advanced cardiomyopathy. Turning to another very exciting molecule, the first-ever inhaled biologic designed to treat a subset of respiratory patients who have traditionally been undertreated.
AZD8630 targets TSLP, and we have just, in the past day, released exciting new phase 1b data at ATS, in which we demonstrate that AZD8630 has an excellent safety profile and was able to provide a statistically significant reduction in FeNO. We are excited to see this molecule move forward into phase 2 later this year. Now, because we know that the majority of our patients are living with interrelated disease, we are designing novel combinations that allow us to address complex conditions such as healthy weight management and cardiometabolic risk. Turning to our weight management portfolio, we are creating a portfolio of molecules that move past short-term weight loss targets and instead focus on healthy weight management, quality of weight loss, and cardiometabolic risk.
Our orally bioavailable GLP-1 receptor agonist has utility as a monotherapy as well as in combination with other small molecules in our portfolio, such as Farxiga or our oral PCSK9 inhibitor. We are excited about our ability to address unmet medical need, and we are moving forward at pace and with a sense of urgency. Also, turning to dapagliflozin, building on the strength of dapagliflozin and expanding beyond monotherapy, we are moving forward with three different fixed-dose combinations in three disease areas across five different indications. This represents one of our largest development programs, and we are excited to announce that each of these combinations is now in phase three. Thinking about the future in immunology, we are working to reimagine a treatment paradigm for people dealing with autoimmune disease.
We have expanded our modalities so that we can build on the strength of Saphnelo, considering Saphnelo and our success in lupus, moving into additional disease areas, as well as additional modalities that will help us to expand the range of diseases that we are able to treat. So our acquisition of Gracell allows us to accelerate our ambitions in this space and gives us the ability to use the autologous BiCAR-T against BCMA and CD19 to address autoimmune disease. And we are very excited to launch a phase 1 study in lupus later this year and are planning for additional indications, to apply with this autoimmune, CAR-T. We are also... If we could just back up a sec, I'm still going at it.
Sorry, sorry.
We're also exploring potential new modalities to use in this space, including allogeneic CAR-T as well as bispecific T-cell engagers. We are looking ahead to also consider resetting the immune system with CAR-T regs. In our partnership with Quell, we're focused on IBD as well as type one diabetes, using Quell's proprietary FoxP3-LOC technology to create smarter, stronger, more stable CAR-T regs. Collectively, we are reimagining the paradigm for treatment of chronic prevalent diseases. I'd love to see the next slide now. Okay, so thinking about today, tomorrow, and the day after tomorrow, in Pascal's words, Pascal has told you about today and tomorrow, and I'd like to tell you about the day after tomorrow. We have a robust portfolio with catalysts across all of our therapeutic areas in the coming years and key data readouts for each of our major therapeutic areas.
Let's focus on the day after tomorrow, where we see that we have a number of exciting readouts to look forward to. Let's take a look at our respiratory and immunology portfolio, in which our systemic biologics continue to gain momentum. Fasenra, Tezspire, Tozorakimab, and Saphnelo all have key readouts moving forward, and we're very excited to see success, success for these molecules in new patient populations, including COPD. For vaccines and immune therapies, the pivotal readout for our new RSV hMPV vaccine is key. And in cardiovascular, renal, and metabolic disease, highlights include delivery of the CardioTransform trial for eplontersen and ATTR cardiomyopathy, as well as three dapagliflozin combinations, zibotentan plus DAPA, balcinrenone plus DAPA, and baxdrostat plus DAPA.
In our weight management portfolio, we are moving forward with multiple assets to address healthy weight management, combined with cardiometabolic risk and organ protection, and we are moving forward at pace and with a sense of urgency. We can do this because we have a strong R&D platform. We have built capabilities across a range of modalities and technologies, as well as deep expertise in our core therapeutic areas, where we remain focused on success... and we look forward to delivering on these critical molecules because we have the capability, with this innovative pipeline and these exciting molecules, to expand treatment for the tens of millions, potentially billion people who need them. We believe that our contribution to AZ 2030's bold ambition and to our continued growth is clear.
Now, my colleagues will tell you more about each one of these things, but first, we have a short video.
At AstraZeneca, we're building on our 40-year heritage in cardiovascular, renal, and metabolic diseases, delivering transformational medicines like Crestor and Farxiga. Yet, a significant burden remains, and it's projected to rise, with CVRM diseases being 4 of the top 7 causes of death globally and 5 of the top 8 leading risk factors of premature death, and the majority of people living with 2 or more of these diseases. Today, we're looking to a future where we can eliminate heart failure and reduce cardiovascular risk from hypertension and dyslipidemia, prevent or slow kidney failure, and reduce and reverse obesity-driven comorbidities. Recognizing the interconnected nature of these diseases, we are establishing a comprehensive and extensive CVRM pipeline through scientific innovation.
Excellent. Wonderful to be with you today. Martin and I are looking forward to sharing over the next 25-30 minutes or so, our cardiovascular, renal, and metabolism strategy. So as you saw in the video, a 40-year history of bringing innovation to CVRM diseases. Today, this therapeutic area is treating over 100 million patients a year throughout the world. The TA is well over $10 billion a year, growing at strong, high double-digit growth, as you see on the left. And what's importantly, as you see on the right, is we continue to strengthen our cardiorenal leadership, predominantly through the success of Farxiga, which has established itself as the foundational treatment across three disease areas of CKD, heart failure, and diabetes. If you look at the middle graph, you see the significant growth year-on-year.
But what's important to recognize behind that, is that that revenue, unlike many products within our industry, that revenue is almost equally divided among the four regions of the globe, between the U.S., Europe, China, and the emerging markets. And what that allows is a couple of things. It establishes a strong platform for the future pipeline of many of the orals, like oral GLP-1 and PCSK9 and others that have broad global potential. But it also allows for a very different type of LOE curve, where beyond U.S. LOE, this brand will continue to deliver significant revenue for many years to come. The second importance of Farxiga to our future pipeline is what you see in that third graph, which is the 8-10 million patients, new patients that we add every year to this medicine, are evenly divided among heart failure, CKD, and diabetes.
The importance of that is, as we'll come on in a moment to talk about our DAPA combination strategy, many of those indications are in CKD and heart failure. In fact, we expect by the time we launch the DAPA combinations, that there will be about 60 million patients globally on DAPA that are, many of them, candidates for one of the combination therapies. So oftentimes we're asked, "What are—who are the patients for which each of your medicines are designed for?" And I think it's a very good question because it is not unintentional, exactly why we built the pipeline that we've built. We're very much focused in CVRM on the diseases where we think and we hear from our physicians, the disease burden is significant, the need for innovation beyond current available treatments is critical, and the populations are large and growing.
Let me walk you through these populations because I think it'll make a lot of sense for each of the molecules that we're gonna share. If you look at cardiovascular, the first column, we're focused on three populations. The first is the ATTR-CM, which is one of the largest cardiomyopathies in cardiovascular disease. 300,000-500,000 patients, growing, significant disease burden, and while there are—there is one mechanism available today, there is a need for multiple more mechanisms. The second is hypertension, and despite all of the many decades and years of hypertension therapies, the reality is the majority of patients are still not at goal, and hypertension is one of the biggest drivers of morbidity and mortality, and there's need for new mechanisms.
The third is dyslipidemia, where despite all of the statins and the statin therapies, and we understand that very well with Crestor, the reality is the majority of patients, despite statin therapy today, are still not at their LDL goal, and ASCVD is still the biggest driver of mortality within cardiovascular disease. Then if we move into renal disease, you see three populations that our nephrologists and our cardiologists tell us consistently and have been for years, "These are my challenging populations. These are where I need innovation." The first is in the kidney disease patient who also has comorbid heart failure. In fact, heart failure patients, 50% of them also have chronic kidney disease. There's four medicines that are guideline-directed therapy for those patients. But when you have heart failure and chronic kidney disease...
The vast majority of those patients are not able to tolerate a particular class, the MRAs, and as a result, are not on guideline-directed therapy. Clear unmet need there. The second population in the middle are chronic kidney disease with hypertension. 75% of kidney disease patients have comorbid hypertension. Along with diabetes, it is the biggest driver of kidney decline. They're more likely to be resistant hypertension, they're more likely to be uncontrolled, and they're more likely to not be as responsive to current treatments. So there's a need to address the hypertensive CKD. And finally, probably the most severe of the populations you see there in the third box are the proteinuria CKD patients, those with significant protein in the urine, which is a sign of significant kidney decline.
It contributes to additional kidney decline, and current treatments in these populations, there are very few therapies that are able to reduce the protein in the urine to the degree that we need to be able to address these patients' needs. So these three patients are clear priorities for us and for our medicines. And finally, as you heard already, the discussion around overweight and obesity, I mentioned hypertension and dyslipidemia as a risk factor. The third, as big or bigger risk factor, is obesity and overweight, particularly in the populations that are carrying comorbidities. And in there, there is a clear need to address the weight, but also to address the comorbidities that live with them. So if we think then about the portfolio that we've built, we've built a very strong portfolio, we believe, of novel, single, and dual mechanisms.
As Pascal mentioned earlier, there are populations for which dual mechanisms are the only way to take the next step of treatment. So if you look at this pipeline, these are the products that we intend to launch before 2030, and they go along with the populations that I just shared with you on the previous page, and we'll walk through each of these populations in detail in a moment. In cardiovascular disease, we're gonna focus on Wainua in ATTR cardiomyopathy, as well as a little bit into the portfolio that we're building in amyloidosis. Baxdrostat as a new mechanism within hypertension, that is, that is the primary mechanism that patients who are still resistant or uncontrolled need addressed, which is aldosterone. Oral PCSK9, which is AZD0780, which we believe is transformative.
It's important not to think of oral PCSK9s in the same space of just injectables in that market. This is going to be like a statin type of breadth of use when you put in the hands of physicians an oral PCSK9. And then in the middle, we're gonna cover the DAPA dual mechanism combinations for each of the three chronic kidney disease as well as heart failure populations. And then we'll finally end with a discussion around our metabolism and our three molecules that will be moving into phase two later this year and into next, our oral GLP-1, our oral or our injectable long-acting amylin, as well as our GLP-1 glucagon and the potential for triples there.
As we walk through these, and as I turn it over to Martin to go through these, you'll see in the top corner what we believe is the potential, the peak year potential of each of these molecules, and we can certainly discuss that in the Q&A section. So with that, why don't we jump into cardiovascular?
Thanks very much, Mina. Great pleasure to be here. So let's talk about Wainua. So this is our antisense oligonucleotide, very specifically targeted to switch off production of the protein that's then deposited in the nerves and neuropathy or the heart of its cardiomyopathy. And we already have launched in the USA for peripheral neuropathy, very good data from the NeuroTransform study. That's doing very well, and we'll roll that out across different geographies. But as a cardiologist, bridging from there to the huge opportunity of unmet need of cardiomyopathy related to amyloid, a particularly severe form of heart failure, average survival only three years from the time of diagnosis. 500,000 people globally, every cardiologist sees these patients, very frustrated because there are so few things you can do to change the future in front of them. So we're very excited about that opportunity.
The more you look for this, the more you find. Recent EPI suggests 500,000 may be a conservative estimate. But why, as a cardiologist, am I so enthusiastic about this? We've got our study in neuropathy related to this disease, and we took the opportunity to take a little snapshot from the NeuroTransform study, and about a third of those patients also have amyloid in the heart. So we looked to the heart, we imaged it throughout that study, and on the right-hand side, it doesn't really matter what measure of cardiac structure or function or the circulating biomarker, NT-proBNP, which relates to cardiac strain, they all went in the right direction, which gives us reason to believe that our very large study, CardioTransform, which is fully enrolled, will be positive, we believe. So let's go on to the design of CardioTransform.
I'm sure you've noticed this. This is the world's largest study in amyloid cardiomyopathy, more than 1,400 patients, and we're comparing using the silencer on top of standard of care with standard of care. We've designed it specifically to run to 140 weeks to give robust evidence to the cardiologists, the prescribers, the patients, and the payers. The primary endpoint in the bottom left, you'll recognize this from all heart failure trials, cardiovascular mortality, and recurrent clinical events. Very robust data answering the question: Does our antisense oligonucleotide, Wainua, make a meaningful difference to these patients?
Moving on to the next slide, though, as Sharon mentioned, we have a whole portfolio of assets that are looking at different mechanisms of action for this large group of patients, and we believe these will be transformational, either on their own or in combination, depending on the severity of the disease, the progression, and by the time they present. So I've talked about Wainua in the top there. That's the gene silencer, switching off production of the TTR protein. Our rare disease unit has a super stabilizer, acoramidis, that you'll hear more about this afternoon. And then very exciting from a cardiologist perspective is the depleter, which is a monoclonal antibody, goes into the tissue, binds to the fibrils, triggers a reaction to actually remove it. So taking the concrete out of the heart rather than just stopping pouring it in.
We believe that we have a portfolio will change guidelines, change practice, and most importantly, change the outcome for patients with this dreaded condition. Let's change the focus now and move to hypertension. Looking around the room, I know a few of you have hypertension, and I bet all your families have people with hypertension. Pay attention to this one. This is really important. There are billions of people with hypertension, and the best will in the world with conventional drugs, many people cannot get to the target. So they know, their families know, the physicians know that they have an increased risk of stroke, of heart failure, of kidney disease, and are really wanting to get to that target. 50% of U.S. patients, for example, have difficult-to-treat hypertension. This is a huge number of individuals.
So Baxdrostat comes into this, one of the first molecules of innovation in this space, which we believe will be best in class, first in class. This blocks the hormone that drives a lot of difficult-to-treat hypertension, aldosterone. And we've seen in our phase II, the BrigHTN study, that when you add this to conventional therapy, you get very impressive reductions in blood pressure. On the right-hand side, you can see placebo-adjusted double digits difference. So something that the physician and the patient can recognize immediately, making a meaningful difference. And that's given us the confidence to go into phase III, which is recruiting well, and we hope to give the results to you at some point in 2025. So very important asset here.
Another one that's very interesting is cholesterol, and statins are very well known, but even with high-intensity statins, 70% of patients who have cardiovascular disease do not get to the modern targets. So there's a huge unmet need in millions, if not billions, of patients across the world. So we have an oral small molecule, PCSK9, underline oral. This is not an injectable. This is a medication you can take once a day, and it's particularly effective at reducing LDL. Now, the results of this, and you can see what I mean by particularly effective, will be presented in Lyon at the European Atherosclerosis Society next week, and I think you'll see why I'm so optimistic about this. We set it up to show at least a 50% reduction on top of statin.
We have confidence, and we have gone into our phase IIb, which is recruiting extremely fast, well ahead of schedule, for the simple reason that both patients and physicians see the absolute need for new solutions in this space. So we're very excited about that asset. But let's frame the DAPA combinations now, Mina.
Excellent. So hopefully in the cardiovascular section, you got a good sense between Wainua and baxdrostat, as well as our oral PCSK9. Let's shift gears a little bit now and talk about the DAPA dual mechanism combinations, in particular in CKD, but also in heart failure, and what is the rationale behind them, and where are we? This is one of probably the most ambitious programs we've done as a company. If you think about three mechanisms across three different disease areas: heart, kidney, and liver, 5+ indications, tens of thousands of patients in these programs. The primary indication, the first indication, is already in Phase III and recruiting very well for each of the combinations. Let's take them from the left and move to the right. So Balcinrenone and dapagliflozin, and Martin will speak much more into the science of it.
But if you think about the populations that we're treating here, the first indication will be in the heart failure, chronic kidney disease, overlapping patients. You see, there's 12 million of these patients between the US and the EU5 markets. That program is ongoing in phase III, and it potentially gives patients the ability to finally be on all 4 guideline-directed therapies, 2 of them in this single tablet. Then we move into chronic kidney disease, broader chronic kidney disease, with MIRA-CKD phase IIb. Then you see in the middle, Baxdrostat, dapagliflozin, which is very much targeted at the chronic kidney disease hypertensive population. We believe between the hypertension benefit of Baxdrostat, the organ-protecting effect of dapagliflozin, that we can make a step change in these patients beyond what DAPA can do alone.
And then you see to the right, Zibotentan and dapagliflozin in two populations where today there are no approved treatments. So you think about CKD with high proteinuria, and the ZENITH high proteinuria phase III program, recruiting months ahead of schedule, very well a sign of just how much physicians need something beyond an SGLT2 alone for these patients. And then liver cirrhosis with the ZILO phase IIb program, where this would be the only treatment for an extremely urgent population to be able to address. You see the size of the populations at the bottom, and what I mentioned on the first slide, I think is important to reinforce, is by the time these launch, we anticipate at least 60 million patients across the globe will be on DAPA monotherapy. And if you imagine a patient, likely many of them will be one of these.
If you imagine a physician being able to tell a patient, "Well, let me take your once-a-day, easy-to-take, simple DAPA and replace it with a once-a-day, simple, easy-to-use dual mechanism that now gives you an additional level of risk reduction and addresses an issue right beyond what you're able to address today," we think it is that simple. Clearly, we see a significant opportunity across each of these dual mechanisms. Why don't we take a little bit of time and talk about the science of each?
... So just to be really clear, these are three very clear patient segments where the science makes sense and there's a big unmet clinical need. So physicians tell us, and I can identify with it, this is exactly the problems that you need to solve for us. And I'm very proud that our teams have gone into Phase III and are ahead of schedule on this. We will produce the evidence base. So let's talk about the first one, and this is DAPA combined with Balcinrenone. Now, this is a mineralocorticoid receptor modulator, so it's a very much more modern version of spironolactone or eplerenone that should be given to patients with heart failure. But half of those patients have Chronic Kidney Disease, and they can't take those drugs despite all the benefits, because their potassium goes up.
You're looking at me going, "Well, what's the problem?" If your potassium goes up, your risk of sudden death goes up, which is pretty serious. So you can see why physicians and patients reluctant to take the old-fashioned drugs. We very cleverly chemistry modified this drug to go in and to give you all the benefits, anti-inflammation, anti-fibrosis, anti-oxidative stress, but really downplay the potassium issue. The reason that we're confident about this is on the right-hand side, and this was presented at the heart failure meeting in Lisbon last week. If you look at here, we took heart failure patients with CKD that also had protein in their urine, so their kidneys were complaining. If you look at DAPA, you get the slight reduction in proteinuria. But if you run Balcinrenone, you immediately see this dramatic improvement in protein leak in the kidneys.
So the organ protection effect of DAPA plus Balcinrenone. DAPA also protects from potassium going up to a slight extent. So you can see the science rationale of putting these together for this subset of patients. It's not a small group, though. 50% of all heart failure patients could benefit from this, and we've taken it into phase III to demonstrate the evidence. So that's the first combination, heart failure with chronic kidney disease, a very specific group of patients. Let's move the focus to another totally different but very specific group. And this is Baxdrostat. I mentioned it for hypertension. Here we're using it to block aldosterone. It blocks the synthesis of aldosterone, and in combination with that, for patients with chronic kidney disease and hypertension, we believe that there will be an additive or synergistic effect for this.
Now, the reason we believe this is if you look at our BrigHTN study, so this is a treatment of resistant hypertension with this agent. And if you look at the patients who have kidney problems and leaking protein into the urine, look at the reduction in the blue bars there of the proteinuria, even at small dose, because this is a highly selective drug. We deliberately designed and took a lot of work to design this, so it very selectively blocks aldosterone without affecting cortisol. It's also very powerful, so it's once daily, 24-hour control, using it in that patient population. Very impressive signals in our phase II of renal protection, and that's why we've gone with confidence into BaxHTN, our phase III study, which is recruiting globally. So I've talked about heart failure with CKD, specific population where the science makes sense.
This is patients with CKD and hypertension, which are absolutely in every nephrologist clinic across the world, trying to control the hypertension, slow the decline to transplantation or dialysis. Let's look at the third very carefully selected population here. This is slightly complicated, so I'll take slightly longer over this slide, with your permission. This is a combination of Zibotentan with DAPA. Now, Zibotentan is an endothelin A antagonist, and we know endothelin is a very powerful vasoconstrictor that narrows the blood vessels and spoils the blood supply and flow within organs. So if you antagonize that with this thing, you actually improve the blood flow within the kidney, within the liver, other organs. It's also anti-inflammatory to that effect. The problem with this drug is it tends to retain fluid, which is what you don't want.
The combination of DAPA, which actually stops you retaining fluid, with Zibotentan, carefully designed to be used at low dose and very effective, very selective, makes perfect sense for two groups of patients. The first one I'm gonna talk about is CKD with high proteinuria. These are patients who live with chronic kidney disease, but are leaking a huge amount of protein into the urine all the time. These are the patients in clinic, you know as a physician, are gonna rapidly deteriorate and are going to need renal transplant or dialysis or gonna die. These are the really high-risk group patients. Very frustrating that they're still leaking so much protein despite standard of care. We published this in The Lancet last year. If you look at the right-hand side, the Zenith study, look at that, 50% reduction in that proteinuria with Zibotentan-DAPA combination.
So something you would see massively with a round of applause by the patient, the family and the clinician by using this agent in their clinic. So I think this is very exciting. We've gone into phase III, and it's recruiting well above schedule. And the reason, again, is because clinicians and patients see the sense of this in this segment. The other group of patients, though, which is often not talked about, is patients with cirrhosis. That's the end stage of a lot of liver problems, such as viral hepatitis, which has been in the news in the U.K. this weekend, but also excess alcohol and also the end stage of fatty liver or MASH. So in those patients, there are no modern licensed therapies at all. No therapies. They do extremely badly, and as the pressure on the liver goes up, they do even worse.
Zibotentan very powerfully drops the pressure within the circulation of the liver. And we believe this could end up, could, we'll have to see how the data plays out, could play out to be the only modern therapy for this large group of patients. 120 million people with liver cirrhosis around the world, and at least 10% of them, the high-risk group within that. So that's Zibotentan DAPA also for two separate populations. So very exciting time. My job to give the evidence to change practice.
Excellent. So hopefully you saw with the DAPA combinations why we're excited and why we believe the dual mechanism is required to actually address each of these populations. So let's shift gears now to metabolism, our final section, and we'll speak a little bit here to our weight management, our obesity, our comorbidity strategy. And as you all are very well aware, this is a significant issue. Half the world's population over time, over the next decade, is either going to be obese or overweight, meaning BMI above 30 or in that 27 to 30 range. What's more important or as important is what you see on the right, which is two-thirds of these patients are carrying at least one, if not multiple, comorbidities, and you see what those are below.
And that's one of the strengths that we have as really a cardiorenal metabolic company with molecules across the breadth, is the opportunity we see. That's why it was so important for us, for example, to find a small molecule, oral GLP-1, that we can combine with our other cardiorenal medicines, because it's all about not just rate reduction, but about managing the cardiorenal, cardiometabolic risk of these patients. So we have 3 molecules in particular that are moving into phase 2 in the coming year. So why don't we go through a little bit of the populations as well as the 3 molecules?
So I think Pascal mentioned this, you've mentioned it. Just to be really super clear, there are three clear populations here. There are those that are very obese, that need to use substantial weight loss and keep that weight loss off, often have comorbidities. So in that space, we have our oral GLP-1, which will be titrated up to high dose. We also have long-acting amylin, I'll mention briefly in a second, but we also have a GLP-1 glucagon, which is a dual active peptide, and we might even have combinations of those, which would give very competitive weight loss for that group of patients that need substantial weight loss, but also control of the long-term risk factors. We also want high-quality weight loss, not losing muscle as well as fat, and that's super important for the long term. So that's one group.
In the middle, larger group of individuals, as Pascal mentioned, are those that are somewhat overweight, need to control that long term, but also have those risk factors, such as hypertension or high cholesterol, et cetera. And there we see lower dose of oral GLP-1 being very effective in that space, and the logic of adding combinations, GLP-1 plus DAPA for long-term super organ protection, but also oral PCSK9 can be combined, which could control your cholesterol and your weight at the same time. And then there's a third group, which is type two diabetes, where obviously oral GLP-1 could play as a role in combination with DAPA, perhaps, but also many of those patients have high cholesterol. So you can see the strategy in these three different groups of individuals of the molecules. But the next slide just gives you a little snapshot of what are these molecules?
So the first one is our oral GLP-1. It's a true small molecule. We've got evidence of strong target engagement in our phase 1 study. Pharmacokinetics suggest it's truly once daily dosing, and it could be combined with other molecules. So one of our suite of molecules to use in this space. Two phase 2b trials will be starting this year, one in type 2 diabetes and one in obesity. So that's oral GLP-1. In the middle, you may not have heard of long-acting amylin, but you'll hear a lot more about this as time goes on. And the reason for this is a very powerful weight loss agent in terms of damping down appetite, in terms of delaying gastric emptying, but it's much better tolerated than GLP-1s, and actually, it spares muscle. So the weight loss you get with this is very likely to be high quality.
So you just lose adipose tissue, fat tissue, rather than the muscle. It could be used for patients who don't tolerate an oral GLP-1 because of side effects, but it also could be added to increase in therapy to maximize the effect. So very high potential for this molecule. On the right, we could combine this drug with our GLP-1 glucagon, and this would be for very competitive weight loss in the extreme end, where you need to lose a lot of weight, but also very good organ protection, cardiometabolic risk reduction, and fat-specific weight loss. So I hope you're getting the message. We have different molecules that could be used either on their own or in combination to fulfill all of the needs of this wide spectrum of patients.
Excellent. And what I will just say as a final comment here is, whether it's oral GLP-1, where we believe we'll be one of the first two small molecules, or long-acting amylin, one of the first two true amylin specific, we think we're very competitive as we come with this portfolio. So to wrap it all up, final slide. Hopefully, you saw the excitement that we have and the energy we have and the belief that we have in the portfolio we're building. Hopefully, you saw at the beginning the clear patient populations that we have made it our mission to find the right solutions for, the small molecules that address each of those specific populations. You see on the left, the clear global growth drivers between now and 2030.
Each one of the medicines we shared with you, we intend to launch between 2030, if the data read out. You see on the right, the data readouts that will guide the decisions as we move through the coming years. With that, thank you for your time, and we'll turn it over to our respiratory and immunology colleagues.
Respiratory and immune-mediated diseases place an enormous burden on patients, society, and health systems around the world. More than 50 years of expertise in respiratory disease has led us to develop transformational medicines like Symbicort and Fasenra, and we're not stopping there. Building on multiple recent launches with Breztri, Saphnelo, Tezspire, and Airsupra, we are reaching more patients than ever before and are transforming outcomes. And we're leveraging our legacy to uncover the true underlying biologic drivers for the diseases we're targeting, including asthma, COPD, and lupus. Using new modalities, we can access previously unreachable targets, and we can identify the right patient for the right treatment in these underserved diseases, offering new hope to those whose conditions have remained uncontrolled by current therapies.
Our bold ambition is to go beyond just controlling symptoms, to slow or reverse the course of disease, to achieve clinical remission, and one day, even discover cures.
Well, good morning, everybody. It is a pleasure joining you today to share with you our growth journey in respiratory and immunology. We thought that probably a good place to start, in light of what Ruud shared with us today, is essentially what is the unmet need that we see in respiratory and immune-mediated diseases. A set of diseases that actually concentrate - one of the most prevalent diseases, ones that concentrate most of the morbid mortality across the world, and those that capture a significant proportion of spend across the world. I think that Ruud painted a very clear picture, looking at some of the stats you see on this slide, that actually a number of these conditions, particularly in the respiratory space, still present a large unmet need.
He mentioned the fact that COPD still remains the third biggest killer, killing actually more people than lung cancer. Unlike cancer, where we've seen a substantial progress, David and Susan will share more, there's been little innovation in this space. Now, there is substantial next wave of innovation coming into the COPD space that I'm sure we're gonna be covering today. You talk about diseases like asthma, and we have tens of millions of patients treated with an inhaler. The bad news is that almost 50% of them won't achieve disease control, which highlights the need to develop new medicines to put these patients in controlling their disease. But even in those that, you know, present a more severe part of the disease, for which biologic has been quite effective, only a fraction of them get access to them.
So a lot more to be done. And beyond asthma and COPD, you see that more morbidity in diseases like IPF and bronchiectasis still are subpar, and, and this is another area in which we're particularly interested in. So against this significant unmet need, we see that this market is poised to deliver substantial growth, and not because of our internal projections, but external projections show that there's substantial growth to deliver in the next seven years, almost doubling the size of this market. As we see more innovation and increased treatment rates and diagnosis rates more than offsetting the LOEs in this space. Now, against these strong market fundamentals, we believe that AstraZeneca is uniquely positioned to lead the way and deliver substantial growth. And what you can see on this slide hopefully captures what we call our thesis for growth in R&I.
If you see the left of this slide, you can see how we've been very busy actually over the last three years on driving a substantial transformation in our portfolio, in which we have left behind the main patent expires we have, and the last ones, Pascal referred to Pulmicort in China, Symbicort in the U.S., but at the same time, bringing significant innovation. As you can see, four launches in the last three years alone, allowing us to drive single-digit growth and are poised to further accelerate into 2030. So the three key pillars of our thesis for growth in R&I, you can see on the right of this slide.
The first one is the fact that we have this now refreshed portfolio that on one hand, doesn't have any major LOE towards the end of the decade, and on the other hand, we have these recent launches that are set to accelerate, and further being supplemented by more than 20 LCMs that we're gonna be covering today, in addition to some NMEs, which is the case like Tozorakimab that Pascal mentioned. Second element, and I think that Pascal painted this very well, is a significant opportunity we see in China and emerging markets, which is probably the region in the world with the highest unmet need and growth potential. And if AstraZeneca is a leader, is more so in respiratory, where we are the number one company in this region.
Last but not least, looking into the future, the very substantial pipeline certainly would be considered to be industry-leading in respiratory, with twice as many clinical programs as our nearest competitor, and now expanding into immunology, both of which will drive further growth towards the end of the decade and indeed beyond. Now, what we summarize on this slide is a little bit the roadmap of the session we're gonna be sharing with you today. And what we have done is to paint for you how we see our portfolio mapped out across the disease spectrum. If you go left to right, you'll see our inhaled therapies, and as disease continue to progress, you'll see our biologics, which are designed to treat severe disease.
We have also indicated our primary indication for these assets, either asthma and COPD, and also some of the additional LCMs we project on this slide. We're gonna be using these to guide you through the presentation. You're probably are familiar with our leading inhaled asthma portfolio with Symbicort and our recently launched first-in-class anti-inflammatory rescue Airsupra in the US, and our fixed-dose combination triple indicated in COPD, Breztri, about which we're gonna be discussing now more in a second. If I take you to the right of the slide, you'll probably be familiar with our severe asthma biologics, Fasenra and Tezspire, about which we're gonna be covering in a second, as well as our phase three asset, Tezepelumab, our IL-33-targeting monoclonal antibody.
Now, I do want to draw your attention to the middle of this slide because as you know, as patients start to navigate the earlier phases of their disease, they're traditionally treated with inhalers. As I was saying before, up to 50% of these patients will remain uncontrolled and at risk. Based on our projections, we believe this is about 20-25 million people by the end of the decade, for which actually there are not many treatments, and only a fraction of these will ever have access to a systemic biologic, which we believe is gonna be between 2 and 2.5 million. So a substantial patient opportunity, which we're targeted to address through the emergence of our early portfolio that Maria is working hard in our labs to develop.
Today, we're gonna be focusing on just one single example of this, and Sharon alluded to that, our novel first-in-class inhaled TSLP, AZD8630, that has the ambition to further expand the Dupixent franchise in this space. So let's dive now into the first asset, which is the case of Breztri. I need to say that we're extremely pleased by the trajectory that Breztri has been showing since its recent launch. Breztri is today the fastest-growing triple, continuing to surpass expectations and very much on track to become a multi-billion-dollar asset for AstraZeneca. Of course, a significant proportion of this growth is driven by the increased share that we continue to deliver across all the markets we serve. But there are three additional growth platforms that we'd like to illuminate for you that will further support Breztri throughout into the future.
The first one is the potential that we see in the further growth of the class, right? And, and as you can see, as of 2023, partially also driven by the launch of Breztri, this class has grown exponentially, right? Now, we do believe that through the emergence of new data we're bringing, as well as the more favorable position that triple therapies have shown in global clinical guidelines, this class will continue to grow, to potentially double its size and become mainstay in COPD. The second opportunity you, you can see on the right of your slide, and it's related to the point that Pascal was making before about what the huge opportunity we see in China and emerging markets.
China is a particular case for us, for triple, because in China, live one in four of all the COPD population in the world, and one of three people who die of COPD actually live in China at the moment. And that is a country in which Breztri is the absolute leader, with 70% market share. Now, on the back of better treatment rates, already for last year, we have seen up to 4 million patients nearly being treated with triple therapies, and we believe that this number can triple by the end of the decade, and many of these patients will be able to benefit from Breztri.
Now, on the back of this significant projected growth, we have made a decision last year, many of you have seen the news, of investing over $400 million on building a state-of-the-art manufacturing facility in Qingdao, in the Shandong province, to supply this ever-expanded demand for our sphere portfolio to supply China and some of the region around it. The third growth platform has to do with the, you know, upcoming now asthma indication that will expand if we want the potential for Breztri, which we expect to read out in 2025. But we're not stopping there, so Caterina, probably you can tell us what else beyond the midterm we have plans for Breztri.
Thank you, Pablo. Thank you for changing the slide. So we are definitely driving a transformation in COPD. In particular, with Breztri, we are really focusing on the cardiopulmonary risk. We know that cardiac and pulmonary factors are driver for mortality in COPD, and we really want to break the inertia that exists in treatment today. If we focus on the left panel there, we have learned from the ETHOS Phase III trial with Breztri, that Breztri was able to demonstrate a significant reduction in the cardiovascular deaths versus LAMA. On the central panel, this data demonstrated that the cardiovascular event are significantly higher following a COPD exacerbation, and actually, this risk persist for as long as a year following the exacerbation. These are recent data that we have been shared with the community from the EXACOS-CV data.
Based on this evidence, we decided early this year to start a very, very interesting trial as a clinician and pulmonologist, which is called the THARROS. It's a Phase III trial which will look at the efficacy of Breztri on the cardiopulmonary outcome, and for the first time, we will combine an endpoint which looks at both cardiac and pulmonary components. If successful, Breztri will give the opportunity, Breztri will be the only triple on the market to demonstrate a significant effect on the cardiopulmonary risk, and this obviously means expanding the use of Breztri to millions eligible patients, but also not only changing the labels, but also changing the clinical guidelines. You understand the impact that this will have on millions and millions of patients, considering what Ruud just stated, that we unfortunately have not advanced in COPD as we wished in the past 20 years.
Thank you, Caterina, and definitely very exciting. But I'll suggest we move now to the more severe disease setting and looking at our biologics opportunity. And we're really encouraged, actually, to see what is the growth potential that we see in this space, particularly around severe asthma, when you look at the progression of the category as a whole, right? And as you can see on the right of your slide, we have seen biologic penetration in severe asthma continue to grow and almost triple in the last seven years on the back of new entrants joining the market, new mechanism of actions which are unlocking new patient populations... and also gaps in the healthcare system being plugged and clinicians more familiar with these therapies.
Now, when you look at the biologic penetration we have at the moment, and we compare that in severe asthma with that achieved in other more mature autoimmune conditions like IBD or rheumatoid arthritis, you see that there is a substantial potential to almost double, if you want, this biologic penetration. Now we believe that this will not only benefit a lot more patients, but also will benefit all the biologic space, in particular, our portfolio, considering the fact that AstraZeneca holds the leading portfolio in severe asthma with Tezspire and Fasenra. Probably we can double-click now and pick in each one of these one by one.
So let me move to Fasenra first, and I need to say that we are extremely, extremely, encouraged to see the double-digit growth in a sustained fashion we have delivered with Fasenra over the last couple of years in spite of the launch of Tezspire. Now, clearly, part of this growth is driven by the category growth that I just presented, but the other part comes from the fact that Fasenra has built a stronghold in severe eosinophilic asthma, being the most prescribed IL-5 in markets like the U.S. Now, looking into the future, we believe there are strong reasons to believe, to actually support Fasenra's further growth, and you can see them on this slide. Now, on the left, one of those growth opportunities, our ability to expand our geographical footprint for Fasenra, enter into China.
And you can see on this slide are the results of our phase 3 MIRACLE study, studying Chinese patients, where Fasenra demonstrated a super strong 74% reduction in severe exacerbations, and indeed, across the different secondary endpoints, and forms the basis of our application for regulatory approval in China, which we expect by the end of this year. Now, if approved, this will give us a significant opportunity to further expand the number of patients we can serve with Fasenra, and certainly consolidate our leadership position in China. And on the right of this slide, even going beyond severe asthma, you see that we have coming fairly soon a set of additional indications, what we call life cycle management opportunities, worth more than $1 billion, right?
of which we're expecting approvals and readouts already this year, and probably for what is the most attractive opportunity, our COPD indication, with our RESOLUTE trial reads out into next year. Now, moving on to our next asset, our recently launched, TSLP-targeting, monoclonal antibody, Tezspire, launched about, two years ago and continued to launch across the world. And I think it's fair to say that we're extremely, extremely encouraged to see the strong trajectory and launch uptake, launch uptake we're seeing with Tezspire, that is achieving pretty much everywhere we launch, a second or first place in terms of dynamic share, only a few months after launch. Now, we believe that this gives us confidence that Tezspire will become not only the broadest biologic in severe asthma, but also the leading biologic in severe asthma.
Even if we believe that asthma is gonna be the main opportunity for Tezspire, we're clearly not stopping there, and we have built a set of new indications that will further support our ambition of making Tezspire a multi-billion-dollar franchise. So probably, Caterina, you can tell us a little bit more about those.
Yes. So later this year, we are expecting results from the phase 3 DIRECTION study, which is our program in severe asthma in China, and also the phase 3 WAYPOINT trial, which studies patients with chronic rhinosinusitis and nasal polyps. Our phase 3 trial in eosinophilic esophagitis is running as per plan, and we are expecting readout after 2025. Last but not least, we have COURSE on the list. COURSE is our phase 2b trial. We have just read out and announced results yesterday in the context of the American Thoracic Society in San Diego. Let's zoom on this. As I just mentioned, COURSE is a phase 2b study in moderate to severe COPD patients, where Tezspire was investigated to examine the effect on exacerbation rate.
We know that Fasenra, dupilumab, and mepolizumab, studied in high eos patients, meaning eos equal or above 300 microliters per cells, which represents around 30% of the market. Tezspire showed nominally significant 37% reduction in COPD exacerbation in patient with eos equal or above 150 microliter per cells, which actually represents more than 60% on the market. In addition, Tezspire also showed numerically significant 47% reduction in moderate to severe in patient with eosinophilic level equal or above 300. So the study was run in a population irrespective of smoking status as well, and we are now looking at exploring opportunity for this indication by imagining the new phase three trial and the next phase of development in conjunction with our partner, Amgen. On the strong trajectory of Tezspire... Pablo, please next slide.
We are now moving into our inhaled anti-TSLP that Sharon just mentioned in her presentation. This drug has really the potential to deliver an efficacy like Tezspire via an inhaled route, meaning that we could actually unlock a number of patients by expanding the population to moderate asthmatic patients, or in addition to the severe ones. If you look at the right panel, these are the data from our phase 1b trial, where inhaled TSLP AZD8630 was able to demonstrate a reduction in fractional exhaled nitric oxide FeNO, about 23%, which is actually equivalent to the reduction that Tezspire showed at the time in the PATHWAY trial. Our phase 2 trial is planned to start in 2024. Now, let's move to another very interesting asset, which is Tozorakimab.
Let me just simplify for you in few seconds how Tozorakimab works. Tozorakimab, if you look at the left panel, is released, is in a reduced form, which signal the ST2 pathway, which cause inflammation. The IL-33 oxidase form also actually signal the RAGE-EGFR complex, which was discovered in our path, in our lab. What Tozorakimab does, block the two pathway, so this is really the differentiator element we have with this compound, by reducing inflammation, yes, but also completely inhibiting this pathway, which is related to the epithelial dysfunction. Not only, what is very interesting that, IL-33 is actually driver of inflammation, but also the epithelial remodeling, and this is related to the mucus hyperproduction. The mucus hyperproduction is a critical feature in COPD patients.
So we believe with this differentiated mechanism, we will be able to act on the mucus clearance and epithelial repair, reinforcing the potential for disease modification that we have with this drug. Based on our proof of concept trial, we have been able to show potential across all EOS level, and also the internal data support efficacy in both former and current smokers. We are currently running a very, very vast phase III trials. The Oberon, Titania, and Miranda are part of the Luna program, which we expect to read out after 2025. We have also a great opportunity with this drug in viral lower respiratory tract disease, and our TILIA study is a phase III study, which we read out again after 2025.
In addition, you would imagine that with this very elegant drug, we are investigating additional opportunity in other respiratory disease.
Thank you very much, Caterina, and indeed, very, very exciting. So hopefully you get a bit of a sense of some of the key opportunities. We went through the inhaled space, the systemic biologic space, and gave you an example in the pre-systemic biologic space. I suggest we pivot now into immunology. I think that if we look back over the last 50 years, we have developed within AstraZeneca a deep expertise, actually, in modulating dysfunction in immune responses, and generally applied into the lung in respiratory. But we're now taking this expertise beyond into other organs and other autoimmune conditions. But we've been very intentional and strategic when deciding where to compete in autoimmune disease, and we have made the decision to build a presence within rheumatology, with particular focus in lupus and some adjacent diseases.
There are a number of reasons why we took that decision. First of all, lupus is an area with relatively limited competition and relatively low innovation. The launch of Saphnelo has become only the second launch in more than 60 years in this space. An area that still remains severely underserved, where with remission rates that can be severely optimized, and access to biologic and advanced therapy is relatively low. And finally, that share with a set of other diseases, relatively common disease drivers, like diseases like myositis, Sjögren's disease, scleroderma, that put together represent as an attractive opportunity as lupus alone, right? And with this in mind, we have now started to build what we believe is one of the strongest portfolios in the industry, with focus in lupus first in SLE.
Our vision for this portfolio when we tackle lupus as a disease is, first of all, to establish Saphnelo as the frontline treatment as a first-line biologic, treating moderate to severe patients. Now, for those patients that we believe that won't be able to achieve disease control, we have now moved into the clinic with our next generation bispecific, targeting pathogenic cells, with which we are moving into phase IIb by the end of the year. Later on in the course of the disease, for those that may remain refractory on the disease, and Shannon alluded to this, we're very excited about the portfolio that our cell therapy portfolio can deliver for these patients, and Caterina will tell us a little bit more now in a second. If I may dive into Saphnelo first.
As you probably know, we have launched Saphnelo only north of two years ago with an IV formulation only. And I need to say, we're very encouraged by the fact that very rapidly in all markets we have launched, we have captured leading market share in almost every market in the IV segment. But we do know that if we want to expand the potential that Saphnelo and this mechanism can bring to patients, we need to develop also a subcutaneous indication. And the reason for that is in the post-pandemic world, this formulation has become very critical, and actually explains the majority of the opportunity, right? Between 50%-80% of the opportunity in the market. So, Caterina, why don't you tell us our plans about Saphnelo moving forward?
Yes. Early this year, we presented the long-term data analysis from our TULIP trial, you can see on the left panel, where we were able to demonstrate that Saphnelo is the only drug to achieve a clinical remission, around 30% actually, at four years. And this is really the only drug on the market. Obviously, as Pablo said, we are really eager to read out, our next trials in sub-Q to really expand and a large population, and not limiting only to the IV, market. And then, of course, phase III Azalea in China is our big program, again, next read out in 2025. But we are not stopping here, actually, because we have a significant expansion that you can see on the right panel by the number of the indication we have-...
Actually already started, for example, phase 3 IRIS in lupus nephritis, or the phase 3 DAISIES in systemic sclerosis, with the data readout after 2025. We are planning to start actually this year with the phase 3 in cutaneous lupus erythematosus, and also in phase 3 in myositis. Next. Thank you. We are also very, very excited by the opportunity we have in cell therapy. Unfortunately, SLE represent a high unmet medical need. One third of these patients actually develop lupus nephritis, which leads to very severe condition, and also death, and 30% of these patients are completely refractory to current therapy. Georg's data demonstrated that it is possible, and this was data in each subject with the SLE, to achieve remission after three months, sustained at two years.
This is, for us, extremely, extremely interesting because there is an opportunity outside oncology to really embark in this indication. But also, we are also accelerating our growing ambition in immunology with the next gen of cell therapy through, for example, the acquisition of Gracell Biotechnologies, and also collaboration with Quell Therapeutics. For example, with Gracell Biotechnologies, we are really have an opportunity with the AZD0120. It's an autologous CAR-T dual-targeted CD-19 and BCMA, and that's, of course, at the moment we have a, an investigator-initiated trial. We open IND in US, in China, with intent really to start our phase trial soon, later this year. With Quell Therapeutics also, we have the potential to be the first-in-class targeted T-reg cell therapy to restore immunotolerance across inflammatory disease, including inflammatory bowel disease and type 1 diabetes.
Good. So I think we've come to the end, and I'll wrap us up now with this one, leaving you with three main final messages. We started this session today talking about our thesis for growth in R&I, and I hope you feel a bit more reassured about that growth trajectory and our contribution to Pascal's ambition for the company. What are the six opportunities in the six franchises I need to watch out for, that will be responsible for the majority of this growth in the years to come? And last but not least, do you feel reassured that actually many of the catalyzers driving this growth are not just happening late into the future, but actually are coming pretty soon, with eight phase three readouts in the next eighteen months alone? So with that, I'll thank you for your attention.
I'll hand over to our colleagues of V&I.
Respiratory infections can cause severe complications in patients with heart failure, asthma, and COPD, and also in patients whose immune systems have been weakened by treatments for cancer or autoimmune conditions. This is why vaccines and immune therapies are a natural fit with our portfolio of biopharmaceuticals, oncology, and rare disease medicines, supporting our growth ambitions to 2030 and beyond. The AstraZeneca COVID-19 vaccine saved over 6 million lives during the pandemic, and we have been protecting high-risk infants from RSV for over 20 years. In 2023, we extended that protection to all infants with the launch of Beyfortus. This has already reduced the burden of RSV on healthcare systems, and we are not stopping there. We are working to deliver more durable vaccines with IVX-A12, potentially the first RSV combination vaccine, and potentially the first vaccine to offer protection against human metapneumovirus, or HMPV.
Infectious disease knows no bounds, and neither do we.
Hello, everyone. I hope. This was deliberate. I hope you still have energy for one more presentation. Marc and I will definitely try to do our best to excite you with the science behind the vaccine and immune therapies, and also share with you our progress. So in vaccine and immune therapies, what we are trying to do is to develop the portfolio of complementary, innovative vaccine and monoclonal antibodies, primarily to protect the vulnerable patient, to protect the patients who are at the highest risk of developing respiratory complications from respiratory infections, but also to the patients that we, in AstraZeneca, take care of across our portfolio. Therefore, we see vaccine and immune therapy unit as a strategic adjacency to our business. Today, presentation will focus on our recent acquisition of Icosavax.
But before that, I'm pleased to share the progress with our two long-acting monoclonal antibodies. Last week, we announced the SUPERNOVA phase 3 efficacy trial high-level positive results, showing that Sipavibart, long-acting monoclonal against COVID-19, demonstrated statistically significant reduction in the number of infections against COVID. And this is important because the SUPERNOVA efficacy trial is the only trial that is run in the immunocompromised population, and we know that those patients are under disproportionate risk of the infection that can also impact their underlying disease. Immunocompromised patients are the patients that we know very well in AstraZeneca. Those are the patients with the hematological malignancies, those are the patients with the solid tumors on the advanced late line of treatments, dialysis, or transplant patients. And we look forward to announcing the full data set at the upcoming medical conference.
Sipavibart, or 3152, is building on our know-how, experience, and heritage in developing long-acting monoclonal antibodies, including a recent launch of Beyfortus for the protection of RSV in infants. Beyfortus is the fastest uptake of any pediatric immunization ever, with 2 million infants protected only in the first season. We are very excited to see the data of the impact Beyfortus has on the infants in Spain and US, showing 90% of the reduction in the hospitalization in the first season. Now, with the leadership of RSV, in RSV, we are very excited with our recent acquisition of Icosavax. This acquisition gives us an access to the innovative virus-like particle, or VLP, platform, as well as an access to the IVX-A12, phase 3-ready combination of RSV and HMPV.
This vaccine is the most advanced in the development, or most advanced RSV combination vaccine, with the FDA Fast Track Designation status. When approved, it has the potential to bring a few novelties into the fast-moving and growing RSV market. It has the potential to be first vaccine for hMPV, and there are no preventive or treatment option for hMPV today. It has the potential to be first combination vaccine with RSV, and it has potential to be first VLP vaccine for respiratory viruses. We do believe that the RSV and hMPV ideal target for the combination vaccine. I will tell you more about that. So I'm sure you all know by now why there is a need to protect from RSV. I'm not sure that you necessarily all know the same for hMPV.
hMPV is actually a less-known cousin of RSV, if you want, but equally very important when it comes to the cause of the serious respiratory infection and hospitalization. Because of the overlapping seasonality, hMPV and RSV together represent 25% of 1.3 million hospitalization in US, and they present a similar level of the hospitalization as flu. Now, you heard today that the population is aging everywhere. So with the aging population, if you look at the middle of the slide, this problem will become bigger because those people of 65+ age actually has significantly higher risk of the hospitalization, is four times higher than influenza. RSV and hMPV are also associated with the most serious disease, a longer stay in a hospital, ICU admissions, and hospital readmissions.
Another important underlying risk factor is the underlying diseases, either in the cardiology or respiratory area. As mentioned, we know that patients very well, and I'm sure you heard that clear and loud today, and treating those patients and protecting them from respiratory infection will really provide the overall holistic improvement of health and outcomes for those patients. We are bringing this differentiated combination vaccine in the already existing clinical pathway. You all know the NITACs, or National Immunization Advisory Technical Committees, like ACIP in US, already recommended RSV protection for older adults. We also believe that, looking at the current vaccination rates in US of pneumococcal and flu vaccines that are above 60%, that you can expect the same for RSV and the combination RSV vaccine.
As mentioned, it is a great combination for the target vaccine because... Sorry. Because, hMPV and RSV have the overlapping seasonality, because they are, as mentioned, cousins with a similar structural biology, and because that unlike flu and COVID, they don't show any seasonal variant changes. We also saw that the external forecast of this market is quite bullish. It goes above $10 billion, and we believe that with this differentiated vaccine, with our global reach, including China, we can reach significant market share. Therefore, we see the potential of this asset being between $1 billion and $3 billion. Next step is the start of phase 3. That is ready to start later this year, and with that, we plan to launch in 2027. Now it's time to look at this exciting science behind this platform.
So, let's see the video, and then over to Marc.
A virus-like particle, or VLP, is a type of vaccine that engages the immune system in a manner that closely resembles interactions with actual viruses. A VLP mimics the structure of a virus, but is not infectious, and hence, not able to cause disease. AstraZeneca's proprietary Icosavax VLPs are made up of a central component that acts as a scaffold. Like an inner structural support system, this core scaffold serves as a foundation that 20 antigen trimers connect to. When combined, these two components self-assemble to form the familiar shape of a natural virus, displaying 60 fusion protein antigens. Unlike soluble, single, or even trimeric subunit antigen vaccines, the multivalent antigen display on a VLP enables stronger cross-linking of antigen-specific receptors... leading to better activation of B cells in the draining lymph nodes following vaccination.
The activated B cells also encounter T helper cells that help the B cells differentiate into both memory B cells and plasma cells. The plasma cells then secrete high levels of antibodies against the VLP, including neutralizing antibodies, potentially leading to a stronger, more durable immune response compared to currently available vaccines.
Great. So I think that video did a really outstanding job explaining why virus-like particles are such powerful immunogens. But for those of you that are interested and would like to see one up close, I actually brought a model of an Icosavax virus-like particle that you're welcome to check out after this session. So as we look forward to starting the phase 3, we're really building upon a strong foundation of data from the phase 2, and let me just highlight a couple key points. Of course, this was the first study to show robust immune responses, not just against RSV, but of course, against RSV and HMPV. In particular, it showed very strong immune responses in all adults, specifically those over age 70, and I'll come back to that in a minute.
These responses were quite durable, in that when we looked at neutralizing antibodies in the serum six months after vaccination, those levels were still quite, quite high. And then lastly, as an immunologist, it was really exciting to see that the vaccine did not require an adjuvant or a compound to boost the immune response. Suggests that the virus-like particles are self-adjuventing all by themselves. So because of these strong data and really the strong platform that these VLPs provide, we really believe that this vaccine is going to have a strong and very competitive target product profile. And let me highlight some of those key features here. Of course, this will be the first vaccine to cover not just RSV, but RSV and HMPV, and importantly, it will have a strong protection in those...
All adults, and specifically those over age 70, where we know both the incidence of disease, and importantly, the severity of disease is the greatest. Because of the durability, we anticipate protection for at least 24 months, and as I mentioned, the vaccine does not require an adjuvant, which means it will have a strong, very good tolerability profile. And then lastly, from really a practical perspective, these virus-like particles are incredibly stable. In fact, they're, they're kind of rock solid, which means we're able to formulate the vaccine in an easy and convenient-to-use pre-filled syringe. And this is in sharp contrast to some of the other vaccines that need to be formulated at point of care and site of use by mixing multiple vials together into a syringe.
So because of that, easy-to-use and convenient formulation, we believe will really broaden, the impact and uptake of the vaccine.
Thanks, Mark. So I hope, you now understand our excitement with this platform and excitement to explore, our ability to bring this vaccine to the patient. It strengthen our late-stage pipeline significantly. It also gives us an opportunity to have $1 billion-$3 billion asset that can be in the market, in the patient hands by 2027. Now, in summary, I hope you heard today that respiratory infections are dangerous. They're especially dangerous for people who are suffering from the underlying cardiometabolic respiratory disease, but also for the patients suffering of oncology or immunology diseases because their immune system have been weakened by their underlying medication.
Again, therefore, we believe that the vaccine and immune therapy is a great strategic adjacency to our business, and it is another important enabler of our growth, until 2030, and, day after tomorrow, as Pascal will say. Thank you very much for your attention. With that, I give floor back to Ruud.
So that concludes the session for Biopharmaceuticals, and hopefully you felt, all of you in the room, the excitement of the presenters and the underlying science and the possibilities we have in our hands. I truly believe we have a proud history in Biopharma. We have seen a fantastic growth in the last few years, but I think someone was mentioning it is also the start of a new beginning, and it also felt that same way for Biopharmaceuticals. You saw a lot of excitement from the CVRM team, whether it is way newer, the very exciting combination products, but equally, of course, also the possibility in order to move forward, in order to help many more patients across the world.
Equally, in RNI, you saw the excitement of the current portfolio, which is a very young portfolio of very important assets, as well as the possibility of Tozorakimab in order to really make a change in the treatment of COPD. And last but not least, of course, the Icosavax acquisition provides us an unique opportunity in order to move into the very attractive H RSV, HMPV world. Last but not least, a lot of attention and a lot of passion about what is happening after 2030. We're already working on new modalities like cell therapy, T-cell engagers, and hopefully in the next few years, you will see more of that. We are very passionate in order to help patients across the world.
If we are helping patients, it's good for societies, and equally, of course, it's also hopefully good for the people who are supporting us, including our shareholders. So with that, I will conclude the session, and I will hand over now to Pascal for the question and answer. If I can ask Sharon and Iskra to join me on the stage as well.
Thank you, Ruud. And so hopefully you see that we execute well, and we try to over-deliver on our goals. We are 15 minutes early.
... and, because we are very generous, we decided to pay you a special dividend and extend the time of the lunch by 15 minutes or so. We'll still extend the time of question and answers by 5 minutes, so that's okay. So who wants to start? Sachin, go ahead. Oh, by the way, just maybe a rule of engagement, if you don't mind. Any questions to do with finance or whatever, if we can keep for later in the day, I'm sure many of those questions will be covered. And if not, we have another Q&A at the end of the day. So if we can focus the questions on biopharma, yeah, I'm sure you saw there's lots of exciting stuff there. Yeah.
Okay, thank you. Sachin Jain, Bank of America. Two prongs of questions on CVRM. So firstly, you gave the target profile and timing of data for the PCSK9. Any sense of timing of the phase I data and target profiles for the oral GLP-1 and the amylin? On the GLP-1, any difference in mono versus combo, and on the amylin, you've been very vocal on the quality of weight loss, so is that something we should focus on? And then on Eplontersen and the Cardio Transform study, just wanted to dig in a little bit more to your confidence in being better than a stabilizer to replace it as mono, and then confidence in it being better as an add-on to background tafamidis. Thank you.
All right, Sachin, thank you for those 14 questions, all rolled into one. Very nicely done, and I really do appreciate your interest in these molecules. So let me start at the beginning. You asked about oral PCSK9 and about our oral GLP-1 receptor agonist. So beginning with oral PCSK9, what we told you today is that we'll be releasing data, shortly later this year on our phase I data, and we have already moved this molecule into phase II. And I think that gives you a sense of our excitement about this molecule. What Martin showed you today is that we set ourselves a very aggressive target product profile, and we said this, this molecule has to be able to demonstrate at least 50% additional LDL-C lowering on top of statins, and we would not move it forward if we hadn't seen that.
We have moved it into phase II, so I think that gives you a sense of what you can expect with our upcoming presentation in the very near future. And when I'm finished, I'll pause and give my colleague, Regina, a chance to offer a little bit more color. With regards to the oral GLP-1 receptor agonist, you asked about, timing of data, and I will repeat, as I have said consistently, that we look forward to sharing those data at an upcoming medical conference later this year. That said, we have told you today that this molecule recently completed a phase I. That was a highly controlled inpatient phase I in type 1 diabetic, or excuse me, type 2 diabetic patients. And that, again, we set ourselves an aggressive threshold to move that forward.
We have told you today that we have planned for two phase IIb starting, studies starting later this year. So that gives you a sense at our encouragement from the phase I data and our ability to make additional investments in clinical development for this molecule.
Amyloidosis.
Amylin. Amylin, then amyloidosis. Thank you for the reminder. So I will hand it over to Regina to tell you a little bit more about our amylin, which is currently in phase I, and we are looking forward to moving that forward, towards the end of this year or early next year. And you asked about amyloidosis and our excitement about our silencer relative to standard of care. And I think Martin gave you a really nice view of why we are so, are so excited about the opportunity for this molecule, not just where it is approved in polyneuropathy, but where it has the potential for approval in cardiomyopathy. And one of the encouraging pieces of data is that, that Martin showed you, which was in our polyneuropathy studies, we recognize that not everybody has just neuropathy, that a subset of patients also have cardiomyopathy.
In a planned subset analysis within that study, what Martin showed you is we saw a significant benefit to cardiac structure and function. So in that study, within a study, we saw very encouraging data, which gives us optimism for our very large Cardio Transform study, which is the largest ever cardiomyopathy study run to date, and which is fully powered to help us analyze the subsets there and really understand the utility of this molecule. We have included patients who are currently on standard of care, which is a stabilizer. I note that patients who are on stabilizer are interested in participating in a clinical study, which gives you a sense that they don't believe that their disease is well controlled on stabilizer alone, and there is additional opportunity to offer them further clinical benefit.
Let me now refer to my expert colleagues in the room. Regina, if you would like to comment on oral PCSK9 and long-acting amylin and offer further color, and Martin, if there's anything that you would like to add to the amyloidosis study, let's start with Regina.
Okay. Thank you so much for the question. So we are very excited about AZD0780, which is our low molecular weight, true small molecule, and this molecule binds to a completely different binding site versus the other PCSK9 inhibitors. So the other PCSK9 inhibitors, they inhibit the interaction between the PCSK9 enzyme and the LDL receptor. This is a huge binding site, protein-protein interaction. Therefore, it's been impossible to develop a true low molecular weight, small molecule to inhibit that interaction. So we have discovered a completely novel binding site on PCSK9. In another part of the molecule, called the C-terminal domain, a small binding pocket, which has enabled us to discover and develop these small molecules, low molecular weight, 400 Dalton molecules. And with this being really true small molecules, means that we can formulate these molecules in a very simple formulation....
with no interaction on food intake, and we can also co-formulate with other molecules to provide these fixed-dose combinations that expand outside of just targeting dyslipidemia and also target other comorbidities that you heard about today in the CVRM presentation. So that's a little bit more color on the PCSK9, and as Sharon said, we will be presenting the phase 1 data next week at the European Atherosclerosis Society meeting. We have progressed rapidly through, I would say, phase 2 B. When it comes to long-acting amylin, so I would just say that the crux with amylin is to have a selective amylin peptide. Because the amylin receptor is a heterodimer with a calcitonin receptor, so other amylin agonists are hitting both calcitonin and the amylin receptor, and that leads to tolerability issues.
Also with having a selective amylin peptide, we believe that we can achieve the fat mass specific weight loss and better tolerability. That is really the key when it comes to the amylin space, and of course, to deliver significant weight loss. Again, improved tolerability, lean mass bearing, fat-specific weight loss. Thank you, and I'll hand over to Martin for Wainua.
Thanks for the question, Sachin. So just to remind you, transthyretin, the protein that's behind amyloid, there's a huge amount circulating. We all produce a lot all the time, so stabilizer makes some sense, you're stabilizing it. But actually, what you want to do is reduce the amount of protein that's circulating, and that's what our asset does, more than 80% knockdown of that. So we believe scientifically that this is a step beyond stabilizing. And just to remind you, in our trial, CardioTransform, as Sharon mentioned, we have 60% of patients on background tafamidis, 40% not, so we'll report out those separate groups. Thank you.
Thanks, Martin. Maybe I could add something to this, Sachin, that is if you look at this TTR protein, of course, you can stabilize it. Makes more sense to stop the production, as Martin explained, but also makes sense to remove the protein that's already there. And it's important to remember that this is a disease, at least today, that is relatively hard to diagnose, and patients are diagnosed a little bit late. And so if they are late, it means they have already accumulation of the protein in their heart muscle. So really, looking forward, it makes sense to remove what's in the heart tissue, and you'll see a video later today from the Ionis team, and then stop the production and so combine the two.
If we do a combination study, and we can show the benefit of combining those two interventions, we'll be the only company with the combination data, and that will benefit, of course, both products. In particular, it will help further differentiate Eplontersen, being the only product with this kind of combination treatment. I forgot to say that, for those of you who are online, if you have a question, please raise your hand button, if you want to ask a question. Oh, so many. Jo, go ahead, sorry. Don't know where to go. Jo, go ahead.
Thank you. Jo Walton, UBS. Three quick ones. Just in terms of the vaccines, you talk about your combination vaccine available for launch in 2027. Is that the start of quite a rapid introduction into a broader vaccine franchise? I feel it's not necessarily particularly commercial, or easy to enter with just one vaccine, so I'm just intrigued about the breadth of your ambition there. Secondly, on the oral GLP, there's a huge amount of debate about whether people can make this sort of stuff in the quantities that's required. Is there something about your one that requires a small dose or something that makes it relatively easy to make? So the question is whether you could really do something at scale. And my third question is just a broad one about early diagnosis.
You talked a lot at the beginning about it's very important if you're going to really tackle disease, to treat people early. Is there anything you're doing that's sort of clever or new in biomarkers or something to improve the early diagnosis so that your treatments actually work better? Thank you.
Jo, many, many good questions. Let me just make a quick comment on vaccines, so we are absolutely clear. Our intent has never been to build a vaccines portfolio like a vaccine company. Our intent has always been to pursue a strategic adjacency kind of approach, if you want. And looking at patients we already take care of, and I think, Iskra said it, patients who have respiratory disease and may experience exacerbations of asthma or COPD linked to a viral infection. Patients who have, say, blood cancer and may be subject to infection, COVID infection, or other viral infections, is very, very striking in our hematology studies, but also other hematology studies from other companies to see the death rate from COVID. Still very high, even though those people are vaccinated.
So whether it's antibodies or vaccine, we really want to focus on these adjacencies and helping patients who actually we already take care of. So we're not, we're not planning to expand our portfolio beyond this kind of very targeted approach. For instance, we're not gonna have a rabies vaccine or diphtheria or whatever. It really is gonna be focused on where we are. Now, in terms of the commercial aspect of the vaccine, maybe, Pascal, you can comment.
Yeah.
And Ruud, maybe you could speak about early diagnostics, the efforts we already have in place. Sharon, you could talk about further science around early diagnosis, but also the nature of the GLP-1 molecule and the manufacturing costs.
Thanks, Pascal, for taking the majority of the question. It's a great question, and it's really important for us to understand that, you know, our strategy that we are building is really different and very specific in the areas where we operate. And therefore, we believe that, you know, breadth of the vaccine portfolio may not be the key success factor for your commercial success. We believe that differentiated, innovative vaccines also built on our experience, both with Beyfortus and the monoclonal antibodies in COVID, as well as understanding and that closeness to the, you know, business in the respiratory or other segments in the company, will give us a competitive advantage and a different edge, if you want, for the commercial model.
We do believe that with the differentiated vaccine we have, if it's the question about IVX-A12, we have an opportunity and advantage to do that.
Remember that, for instance, Merck does very well with an HPV vaccine without having a whole range of vaccines like Sanofi or GSK would have. So it is possible to do well if you have differentiated the vaccines and, of course, put together a good commercial plan. But-
Yeah, quickly, responding to your question about early detection and diagnosis. One of the success stories of Farxiga clearly is that we have very substantial programs in place for early detection of CKD. It's relative. The moment you are losing protein, if it is in the urine, it's relatively easy to detect. So one of the success stories clearly in China is that we have, I believe, now screened more than 50 million people in China. And of course, then you pick up a lot of those CKD patients now, and we will continue to do that. In the asthma space, it's equally, it roughly takes 7 years before a severe asthmatic is diagnosed.
So we have programs, patient support programs in place in order to detect much earlier those patients, so they will move from primary care into specialty care, and that's a big part of our, let's say, commercial efforts as well as medical affairs efforts, I need to say, in order to really change the way healthcare is delivered. Equally, of course, in amyloidosis, Sharon and the team and the research team are looking for, is it possible to detect, for example, those misfolded proteins in the blood? So a blood test. So those activities are also ongoing from a research perspective.
Great setup, Ruud. So I'll add to that. As Ruud told you, we are working on the very exploratory approach to be able to identify a soluble biomarker for amyloidosis. That's technically very difficult. In the near term, what we think is more achievable is building an AI algorithm that is shareware, that allows the echo diagnostician to get a red flag for cardiac wall thickening, which signals that this patient may have amyloidosis. We know that patients who are diagnosed late in their disease have an especially poor prognosis, and that's at a point where stabilizers are unlikely to help them. So if we can bring that diagnosis back earlier, we can offer patients a better health outcome, and so that's been a focus, which is a collaborative effort between the biopharma team, as well as our colleagues in Alexion.
Your other question was about GLP-1: Can we make it at scale, and what are we doing to be able to address that? And I'll get started, and then I'll hand it over to my colleague. So I think a number of people have recognized that these molecules in the class tend to be on the larger side and therefore have complex synthetic routes. We identified opportunities almost immediately to simplify the synthetic route for AZD5004, and we have been working in collaboration between our outstanding team in AstraZeneca, together with our colleagues at Eccogene. We think we've already made substantial inroads, and Elisabeth, who is leading this project across the range of development efforts, has put into place a very aggressive plan to ensure that we have the supply that we need. Would you like to add more color?
Yes, I can definitely do that. So when I took this on in the beginning of the year, I had the same fear that maybe CMC would be sort of the limiting factor here. I can tell you it's not gonna be that. We have a fantastic CMC team, and we will be able to deliver both the clinical supply to whatever aggressive clinical plans that we are doing, and a commercial supply in the end. Also, please remember, this is a small molecule, which is really good from many perspectives. Not only does it make it easier to produce, but it also sets the foundation for fixed dose combinations. We will be able to combine with this molecule, with other great molecules that we have in the area of cardiorenal protection in our portfolio.
That is the beauty of a small... of an oral agent and a small molecule. You can manufacture it at scale much more easily than an injectable and so small molecule. You can bring it to millions, hundreds of millions of patients around the world at lower cost. Of course, at a level, price level, we can still be profitable, for sure, but at a lower pr- a lower cost, make it more affordable, and avoid hundreds of millions of plastic pens being put in the rubbish bin every day. So there are lots of benefits to a to an oral agent, and of course, the combinability is a critical part, yeah? There's one here and one behind, and then we'll go there. So, and there's James, and then we'll move to the left side. Is that okay?
... Hi, thanks. Emily Field from Barclays. I just wanted to follow up on, on the point on weight loss quality, as this is obviously being discussed more as a point of potential product differentiation. You know, do you see this as being an approvable clinical endpoint? Or just, you know, how are you gonna be able to, you know, perhaps add this claim to the label? Will this be intended for development in specific populations, such as the elderly? And then maybe a question on COPD. Ahead of potentially the first biologic launch later this year, Tezspire would still need to run a phase three study, and then Tozorakimab's phase three data could potentially come after two competitors in the class. So just how are you thinking about commercial differentiation here?
Is it the potential to be addressing broader population sets, as the course data from yesterday would suggest? Just any further color there. Thank you.
Could we ask maybe Elisabeth, do you want to take the first one? And
No.
Or maybe Pablo or...
Sorry, COPD?
Yeah. Let's start with maybe, Elisabeth.
Yes. You asked about sort of quality of weight loss and how we are gonna measure that, and then what it will mean for the label, and so forth. I think the registrational endpoints in this area is going to remain being sort of the amount of weight loss that you are having, but that's not gonna be enough. We will need to show clinical outcomes data, be it in the cardiac space, in the renal space, or in other space. I think as part of these trials, be it the registrational trials or the longer-term clinical outcomes trials, we will need to show sort of the quality of weight loss in addition to just the weight loss numbers.
So I can see us move away from just looking at numbers, but instead looking at both quality and what kind of other cardiorenal endpoints do we affect. And we are very likely to get into a place where it's not just the magnitude that matters, but also how you decrease it and what impact you have on other parts. And I think that's what we will be doing with our development programs in this space.
And then to the question you had around differentiation in COPD biologics. I think that, first of all, an important premise is that, sometimes we think that with some of these diseases, and clearly that is not necessarily very helpful in COPD, we think that we can put, you know, medicines in boxes. COPD, as you probably know, is a highly heterogeneous disease, right? And we call COPD a raft of probably sub-patient populations and biology drivers that we probably don't understand yet, right? So it's quite likely, and we believe that some of the way that some of these diseases and autoimmune diseases evolve is a good marker to how we see this market approaching, which you'll need more than one mechanism to potentially achieve disease control.
Remember this, we're talking about the third biggest killer in the world, right? So the mandate is there, and you probably need more than one mechanism to do that. Now, at the moment, the only relatively simple marker that we have found to drive activity is eosinophil levels, for instance, although that may be a blunt tool in the future, and certainly, as the science develops, we learn more. Now, when it comes to that point, you know, we do have a primary marker of activity with Tezspire, and we presented this data now. So we do know that the drug seems to be active in eosinophils 150 and above. Remember, this is two-thirds of the patients, right?
Which is, you know, a very big, if you want, differentiating factor, and probably confirming the broader mechanism of action that we can achieve with the TSLP relative to other eosinophilic agents. When it comes to Tozorakimab, I think that Caterina did a great job on explaining why we believe that the dual mechanism of action on targeting not only inflammation, but the oxidized form, can probably provide differentiation, particularly working around the mucociliary clearance element that is so prominent in the COPD phenotype. Now, beyond that, I mean, the data will be the data, right? So we need to wait for phase three. But the fact that we believe that Tozorakimab can act across the broad eosinophilic spectrum, and at the moment can target current smokers and former smokers, if confirmed in the phase three, could be additional elements of differentiation.
Sorry. Let's keep going there. Yeah. Then we'll go to James.
Thanks very much for taking my questions. Christopher Uhde from SEB. My first would be on the Icosavax. And, I guess there I'm wondering... I mean, you have a vaccine that looks like it's probably very competitive on the RSV specifically, but then you also add in the MPV.
I guess I'm wondering, if you're saying $1-3 billion in potential value for something that's, you know, roughly twice as much value, I should say, than what's out there, and the market's obviously quite a bit bigger than $1-3 billion, how much do you leave on the table by having the commercial strategy that you have, you know, of not having primary care access instead of, yeah, at the same time as you get the first pass in specialty care?
It's a great question for Iskra-
Yes, it-
because the ambition is actually more than that. But go ahead, actually, answer the question?
Thanks for the question. So let me first reassure you that we are not leaving, we are not going to leave anything on the table. But equally, you know, this market is relatively new. We know that there will be a number of players in the next, you know, 5+ years, and we believe that, you know, as I mentioned, we will reach the reasonable market share. Now, how big will be the market will probably drive the final peak year sales. But you can say that we were a bit on a conservative side with the estimation that we currently have. We will definitely utilize everything that is needed to, A, get access.
We know NITAGs and ACRP, we have a huge experience with Beyfortus, so we definitely know how what needs to happen to get the access in US as well as in other markets across the globe, and we will definitely leverage the huge footprint, not only in US and Europe, but also in China. And I can assure you that we are already discussing and, and, you know, preparing for the access that will be broad, and it will go across China and emerging market. So nothing will be left on the table.
Yes, nothing. James? Sorry, and then we'll take, we'll move across to left after James, if, if I may.
Hello, James Gordon, JPMorgan. Thanks for taking two questions on biopharma. The first one was oral GLP-1. So I saw you're starting a phase IIb this year, but am I reading the slides correctly, that it looks like that does have $5 billion+ peak sales potential, but that's not in the 2030 target? So that's something that would happen further out. And is the reason for that, that the real potential is as combos, so it might have quite a lengthy development program. So it looks like you're targeting that as a post-2030 contributor, really. And the second question was on Tezspire or COPD. So I think I heard a comment that for Tezspire, COPD is more modest potential, and toza is the big product.
But for toza, is the excitement on the first two phase III you're running, or is it, do we need to be a bit cautious there, and it's really the, the third phase III that you started more recently, that, that you think that's the one that's gonna make you have the big product in COPD?
So maybe I can cover the first one very quickly, actually. The GLP-1 actually contributes to the 2030 target, but what we wanted to signal is that it's smaller, and most of the growth will come post-2030. You know, there are... as you can see, there are lots of assets, and we try to give you pointers as to what would have a substantial impact on 2030 and what had a substantial impact on the peak year revenue as it relates to the oral GLP-1. The big peak year revenue is post-2030, but it will definitely launch before 2030 and contribute to 2030 goals, yeah. Who wants to go the second one?
I'll start the second one, and then Caterina can finish up. So your second question was about Tezspire and Tozorakimab, and the LUNA program in Tozorakimab. I sense that you were sort of reading between the lines and trying to understand if we favored one molecule over the other. So let me just reframe that narrative a little bit in the way that I wish that I could bring it across. So, as Pablo mentioned, we don't think of COPD as a single disease. We think of it as a heterogeneous, complex condition. It is the third leading cause of death. 400 million people worldwide are suffering from COPD, and we know that we need multiple mechanisms to be able to treat that complexity.
So the data that we released yesterday for Tezspire, in collaboration with our colleagues at Amgen, demonstrates activity for Tezspire across a range of eosinophils, and we saw a significant or numerical reduction in moderate to severe exacerbations for patients with over 150 and over 300 eosinophils per microliter. So I think that's really encouraging data, and based on that, we're actively planning for the next phase of development. At the same time, we're progressing Tozorakimab, which, as Caterina and Pablo explained, has a really beautifully differentiated mechanism of action that we think is addressing aspects of disease that aren't covered by a TSLP blocker. And so we are excited to see those data read out, and we have three studies ongoing at the same time, and you asked for a little more detail there.
And so I, I think we've been very open about the fact that we began with Titania and Oberon and then added Miranda to further expand the dosing regimens, so that we could fully explore the activity of this molecule and really optimize the utility for that for future prescribers, one would hope, and the data will tell us what we need to know. But we remain very excited about the potential for this because we think it addresses aspects of the disease, and Pablo hinted at that, not just reduction of inflammation, but also mucociliary clearance and epithelial remodeling. And with that, I'll hand it to Caterina to add any additional color.
No, I think I have nothing to add to that, except really highlight the fact that we remain confident Oberon and Titania will show efficacy with the molecule. We are just complementing with Miranda to really expand the full potential of the molecule.
Maybe one last general comment before I go to the next question, that you make me think of, actually, James, is, again, our $80 billion is risk-adjusted, and so all the projects are, are risk-adjusted. So we take all the projects, and we all risk-adjust them, and then we look at how they contribute to 2030. Of course, if a product, or project works, then they are, they become much bigger. So the old GLP-1 and what we've told you, you have got to think about in our forecast, it's risk-adjusted, but it will grow immediately, as soon as we know it works and, and it succeeds. Do we have a, a microphone there?
Matthias Häggblom, Handelsbanken. Two questions, please. So one, one of the opening slides you showed, Pascal, the bridge to the $80 billion target by 2030, seemed to show the magnitude of growth from existing portfolio, which appeared larger than the magnitude of benefit from risk-adjusted sales from your new medicines. Is that the right way to think of the contributions? And then secondly, thanks for the transparency on the peak sales potential per asset, but we don't know your risk adjustment per asset. So is there any particular asset that we've covered so far where you think probability of success and perhaps not only the potential is in particular underappreciated? Thanks.
Can you help me with the first question, so I'm sure I answer the correct?
I think the question was that the arrows on the chart-
Yeah
... that you showed, the existing product arrow looked bigger than the contribution-
Ah!
from the NMEs.
Sorry. All right.
Is that reflective of where the revenue's likely to come from?
Yeah, don't read too much into this, the cosmetics of the arrows. We went back and forth on the arrows, but they're not meant to represent that one bucket is growing more than the other. They are really directional buckets. In terms of the risk adjustment by project, we can't, of course, tell you every single aspect of our forecast. So this one, you know, it's hard to answer, and you'll have to figure out yourself really what the risk adjustment is for the various different products, yeah.
Maybe if I can add on the first bucket, which was the existing products, it's actually almost two categories within those existing products. There's existing products with existing indications, you know, the Breztri, et cetera, which are still very early in their launch and still have a long trajectory to go. And then there's the existing products with new indications, and you'll hear in oncology and all the indication expansions and so on and so forth. And those life cycle managements are probably lower risk from a risk standpoint, if you were to risk adjust it. And then the third category, which is the NME, are probably slightly higher risk. But again, you know, the risk adjustment, there are industry standards for what is the risk adjustment for a phase one or a phase two or a phase three.
And then we, based on our knowledge, and experience with the molecule and data we know, we may up or down modulate, but that hopefully gives you a good context.
The only thing I would say that historically, our pipeline has delivered, on average, a better than our probability of success was in our plan. So, because essentially, as Aradhana said, we adjust a little bit the industry sort of average, but not that much. We are close to the industry average, and in fact, reality has been above industry average, so the reality of our delivery has been better than what we planned for.
Thank you. It's Luisa Hector at Berenberg. On obesity, based on your timeline, how confident are you that you will be running placebo-controlled phase III trials across the portfolio? And then maybe just a broader question on pricing, because you've talked a lot about combination therapies. I know you've got different examples of Farxiga, which will be generic, and then more novel combinations and the vaccine. So how have you thought about pricing, in terms of one plus one is two, or maybe not?
Yeah. So that last one, 1 + 1 is 2, is certainly not what we're aiming for. We are clearly aiming for a level of differentiation, and then, of course, the clinical studies, they need to show that. But if you move into relatively highly specialized areas like kidney disease, we're aiming for a relatively high price per day. And of course, if the data will come out, we will make sure that we will create so-called value packs, value stories for our payers. But the whole assumption is that those combination products will be well-priced and above, of course, far above the generic Farxiga.
The price, we always set the price based on the clinical benefit we deliver and, you know, the cost effectiveness of the intervention. So when you look at patients that Martin described that have high level of proteinuria, they are very likely to progress very quickly towards transplantation or dialysis. Of course, the clinical benefit, if you deliver a good benefit, the clinical benefit justifies a higher price. On the other hand, if you deal with a very large population of patients, where essentially, you know, it's gonna be harder to justify the value, then you adjust your price differently.
But that's the beauty of the fixed dose combinations, is that you can bring a product with a broader, clinical benefit because you have two medicines in one, and then price it at the right level rather than have two medicines at different prices.
Right. I think there was also a question in there about 5004, and I think you were reflecting on the competitive landscape and asking if by the time we get to phase III, we would be running placebo-controlled trials. Excellent question, and I'll hand that to the clinical development expert, Elisabeth.
Thank you. It is a very good question. Our assumption is that at that time when we are starting phase III with the oral GLP-1 that we have, AZD5004, we will be able to run those studies, placebo-controlled. Of course, over time, this will evolve, and if we go into patient population with a really high unmet need and very high obesity, high BMI, and you might need combination treatments, in the end, that's a different setting. But for sort of the approval for AZD5004, our anticipation is that we will be able to do that placebo.
The number of patients, as we all know, in this space is still extremely high, so.
Is it me or is it? Okay, I'll go. Emmanuel Papadakis. I'll save the dividend question for later. So maybe a couple of product-specific biopharma questions. Just to follow up on your answer before, I didn't really understand. I mean, you can't really make a strong compliance argument in many of those larger indications, CKD, et cetera. Why would anyone pay more than the generic price for the dapagliflozin component of a combination molecule? If you could just elaborate on that, that'd be helpful. And then two of the combination programs, Balcinrenone, you know, earlier endeavors to replace first, second generation MRAs haven't succeeded spectacularly well. It doesn't look like you're running a head-to-head study.
So perhaps you could just give us your target profile for the rate of hypokalemia you're hoping to show in phase III, and whether you think you will need to do a head-to-head study. Then on Zibotentan, the phase II was impressive, but we did see edema. We saw double, I think it was actually triple the rate of discontinuations versus placebo. So labeling, do you expect to see anything?
... typical for endothelin receptor antagonists on the label that would restrict the addressable population? Thank you.
Great question. Maybe Martin, you want to take those. That's another beauty of the combinations with DAPA.
Yeah. So for Balcinrenone—Sorry, I don't remember who was asking the question. Balcinrenone, these are patients who don't tolerate first- or second-generation agents, so it wouldn't make sense to randomize patients back onto a drug we know they've failed on. So we're not planning on doing a head-to-head comparison. We think it's a very clearly identifiable group, and we think we can identify them and put them into the trial and show the benefit. In terms of the potassium profile, we're hoping to be very competitive on that front, and the data's been published from a miracle study that you can read.
And Zebetaantan?
Zibotentan, yes. So that also, there isn't really a competitor in that space. These are patients who have heavy proteinuria, despite standard of care, such as ACE inhibitors. So we think that's a group where Zibotentan and DAPA will go together, and that's what we tend to do in the study. I'm not sure if I completely answered that question.
Yeah.
Let's go.
I mean, I guess what I wanted just to add is, the hope here or the belief is DAPA will also help reduce the risk of hyperkalemia and reduce the, in the case of the Zibotentan, reduce the edema, and that's what we've seen before, and that's the beauty of combining the two again, is that the potential edema you see with Zibotentan will be managed down by the combination with DAPA. Do you want to cover the price?
Yeah. So, perhaps Mina can give a little bit more flavor because we have done extensive market research. But just for the audience, those combinations are unique, not so much because of the typical flows of components, which will be generic over time, but it is a unique patent-protected molecule in that combination, and that combination in itself will be priced according to the clinical effectiveness.
Yeah, exactly. If you think... Is my microphone on? Okay. If you think about Forxiga alone, it—even though now it's in CKD and heart failure, it actually initiated in diabetes, and it's priced as a diabetes medicine. As you know, the pricing of diabetes therapies is very low compared to CKD and heart failure. And the new indications that are coming in the case of Balcinrenone DAPA or Baxdrostat DAPA, et cetera, Zibotentan DAPA, are in CKD and are in, and are in heart failure, and in some cases, more difficult to treat CKD population. So it's a very different price equation, and DAPA's price is not really a factor within that combination.
It's really what you're bringing as the innovation to that dual mechanism, whether it's Balcinrenone, whether it's Baxdrostat, whether it's Zibotentan, that is really bringing a very different price, to that dual mechanism than the addition of DAPA plus, if that makes sense.
Compare it, to make it very simple, compare it a little bit with Entresto. The price of Entresto is not driven by Diovan valsartan. So it's the combination of this new molecular entity.
In terms of hyperkalemia, our expectation is that valsartan DAPA has no greater hyperkalemia than DAPA alone, and that's the promise of that combination and why we think it, if it delivers against that, becomes so compelling in the heart failure CKD population.
Thanks, Mina. I'm starting to be given a hard time by Andy and Aradhana, so we're gonna have to close here, if we may. Is that okay? So we'll break for lunch, and you're more than welcome to wander around to our cafeteria. If you want to go out there rather than have lunch closer to this room, just go around, and then what time do we meet again? 1:25. Okay. See you soon.
Globally, more than 400 million people live with a rare disease. Of the over 10,000 known rare diseases, around 90% do not have an approved treatment. At Alexion, AstraZeneca Rare Disease, we were the first to translate the complex biology of the complement system to deliver treatments for multiple rare diseases. Today, we have 6 medicines approved across 7 rare diseases, including paroxysmal nocturnal hemoglobinuria, generalized myasthenia gravis, and hypophosphatasia. We continue to strengthen our clinical stage pipeline, expanding into new complement-mediated and adjacent diseases, and exploring new targets beyond complement. With roughly 80% of rare diseases genetically driven, we are also investing in transformational technologies such as genomic medicines.
Fueled by innovation and leveraging the global reach of AstraZeneca, we have the potential to transform the lives of even more people living with rare diseases around the world, creating meaningful impact for the more than 400 million people in the rare disease community.
Good afternoon, and welcome back from lunch. We are delighted, Gianluca and me, to be making this rare disease presentation. The first slide will show you a flashback to the announcement that we made at the time of announcement of the Alexion acquisition. And we said on that day that the rare disease would help or contribute to the growth of AstraZeneca through 2025. And I think the numbers that we will show you in a second are going to demonstrate that we indeed did not dilute the growth of AstraZeneca. So Alexion is very pleased to have, you know, contributed to the growth of AstraZeneca. On the right, we have just summarized and simplified our strategy. Our strategy is to continue to be the leader in the complement.
Complement, we have leadership in hematology, nephrology, as well as neurology. Now, the second avenue for us is to go beyond the complement, because obviously there are many other rare disease which are not accessible to the complement, and there we focus on first-in-class or best-in-class medicine. The areas that we are going through are bone disease, endocrine rare disease, as well as amyloidosis. We had this morning some reference to our depleter in the transthyretin amyloidosis, but we have also another depleter in light chain amyloidosis that Gianluca will describe for you in a second. Longer term, we have at the bottom the technologies that we want to invest in, and obviously we're going to try to find transformative and potentially curative medicine, and in particular, in gene therapy.
On the left of this slide, you have the performance for 2022, as well as 2023. The loss of exclusivity of Soliris, but we are counteracting this with a very rapid conversion to Ultomiris, and in most indications where we have double indications, we have already a conversion above 80%. Ultomiris is going to grow, and I will explain this in a minute, through larger... more indications, but also a very strong regional expansion. And then you have several key NMEs, which are listed on this, and we will go through them later on. This is basically the first thing. I wanted to talk also to the topic that we discussed at the time of the announcement, which was the sustainability of, or the robustness of the growth of Alexion.
And I think you can see on the left, first, the revenues, and on the right, the patient growth for Alexion in the last two years and some. And you can see that the growth, both on revenues, but also more importantly, maybe on the patient, is very robust. You can see this acceleration of the patient reach. And it's important to put in perspective these two metrics, the revenues on the left and the patient growth on the right, because we have several effects within our portfolio. We have obviously a product mix. We are enlarging to different population, and we also have a geographic mix. We are expanding in many other countries, which have a lower price than maybe the key countries where we were present in two thousand and twenty or twenty-one.
So it's important to keep in mind both this product mix effect as well as this geographic mix. I get now to this slide, which talks first of all, about the regional expansion, and it's a very important growth factor for us. So Pascal, in his first slide this morning, introduced the compounded growth rate of a rare disease since 2019 to 2023, and you may remember that this growth rate were 22%. But if you look post-acquisition of Alexion, you see this growth rate is, you know, much stronger, in particular in 2023 and first quarter of 2024. At the bottom, you have the progression of our reach in terms of countries. At the time of Alexion, before the Alexion acquisition, Alexion was present in 20 countries.
20 most important countries, probably, but only 20 countries. We are now currently present in 70 countries, and our ambition is to reach 100 countries by the year 2030. On the right, we have a small vignette on China, where the products of Alexion were not present until the acquisition, and then, Alexion has been able to leverage the very strong presence of AstraZeneca in China. AstraZeneca has a strong presence for the last 30 years, and we could leverage that strength to rapidly get our product registered. But also, and you see at the bottom, it's extremely important, the listing on the National Drug Reimbursement List. So now we have 2 products, indicated, Soliris in several indications and Koselugo in NF1.
These two products were launched in 2022 and 2023, and then we received the National Drug Reimbursement Listing in January of 2024. So we are now in this NDRL listing, and both products are doing very well, and we are gaining patients every day. So now I'm going to turn to the complement, which obviously is the main franchise of Alexion. So if you look at the in a similar fashion, the sales revenue growth for the C5, you know, this is this constant growth, seven, eight, and 10%. And then, more importantly, at the bottom, we have tried to analyze the growth, the cause of the growth of the patients.
You can see that at the bottom, the ultra-orphan indication or the legacy indications of Alexion continue to grow over this period. But it's also very important to see the dramatic growth of the neurology indication, which we first obtained with Soliris in 2017, and more recently, in 2022 with Ultomiris. And basically, the reason of this continual growth in the number of patients is, one, the superior efficacy of the C5 inhibitors. They provide a very rapid and sustained inhibition, but... And also, very importantly for the neurology indication, they enable physicians and patients to reduce the steroids, and some- in some case, eliminate the steroids, and that's extremely important for the neurology indications. I described earlier on the geographic reach.
It's a very important growth factor for, for us, and longer term, the expansion of indications for Ultomiris will be important. We will cover that topic in a second, but these are the reason. At the top, you have the rapid conversion, as I mentioned earlier on, from Soliris to Ultomiris. You will all remember that the price of Ultomiris is about 30% lower than that of Soliris, so... But longer term, obviously, this provides a, a greater robustness in our portfolio as we expect the entry of biosimilars. So I'm turning now to neurology. So neurology, you can see the growth rate, both in revenue as well as in patient growth, is about twice as fast as what we have seen for the overall C5, and this is due to the extreme performance or, or strength in neurology.
In particular, Ultomiris had, after three years, results were showed that we have 88% of patients with clinical meaningful improvements. So the objective of the treatment is to sustain the control of symptom over time, to avoid the patient goes through various cycles, and Ultomiris provide you this stability of efficacy. Most guidelines nowadays also talk about the need to spare the steroid or reduce the use of steroid, and in 75% of patients, after two years, 75% of patients can have a low dose of steroid after two years. This is now more and more indicated in every guideline of the world. There is a competition with the FCRN, and usually, they gain a lot of naive patients from unbranded.
But if we just look at a very interesting metric, a dynamic metric, the switch to FCRN or the switch from FCRN, since late third quarter of 2023, we have been gaining more patients than we lose to FCRN. So continuing on, myasthenia gravis. So basically, Soliris, historically, Soliris was first approved as a pioneer in this indication in 2017. We then launched Ultomiris in 2022, and Gefurulimab is our third-generation C5 inhibitor, presently in currently under development. And it's a subcut formulation. It will be a weekly subcut formulation, so this will be an easier treatment in comparison to the IV. If you look on the panel on the right, you look at historically, Soliris started with gaining very refractory patient for the most severe population.
And then with the introduction of Ultomiris, we enlarge the patient population. It's so less severe than what Soliris was, and with Gefurulimab, we will further increase the patient population. The three class of products will certainly continue to expand the usage of branded medicine in myasthenia gravis. And to provide you some perspective of that, we have prepared this slide where you have today a current usage of branded medicine, ours, and that of competitors, which is probably in the 25% or 30% currently. We expect the branded medicine to occupy about 80%, in 10 years from now. So there will be a very rapid increase in most developed countries of the use of branded medicine in myasthenia gravis at the expense of steroids and immunosuppressant.
Today, our products are launched in 31 countries, so, you know, a good job has been done, but there are still 25 more countries where we expect to launch by 2025. And again, as I said earlier on in the... It's extremely important that the guidelines of most countries now do talk about the control of symptoms, but talk also about the necessity to reduce the steroid usage, and this is where Ultomiris and the other C5 inhibitors have a benefit. I will now talk to the extension of indications for Ultomiris. We start on the left, this dark red panel, where we describe here the legacy indication, atypical HUS as well as PNH. And then I was just talking about the pioneering work in the neurology indication, myasthenia gravis and neuromyelitis optica.
You have on the right of that, you have a series of other indications, which are mostly renal indications or transplantology. We will, and Gianluca will, in a second, talk to you about hematopoietic stem cell, as well as IgAN. But we have also other trials, as you can see, in lupus nephritis, AKI, and delayed graft function for renal transplant. We will talk about those indications in a moment. The clinical trials that we have on the right are ongoing, and their data readout is planned for 2025 for ICTTMA, and for Artemis and ICAN, the data will come post-2025.
So we have seen, and we are going to see for several more years, the growth, which is fueled by the neurology indications, and the further, the next wave of growth will come mostly from the renal indication as well as the transplantology indications. Gianluca?
Thank you very much. Thank you, Marc, and good afternoon, everyone. So I'm going to talk about the first of our catalysts, which is our phase III efforts with Ultomiris in thrombotic microangiopathy following hematopoietic cell transplant, or HSCT TMA. It's a very severe condition, it's a rare disease, life-threatening complication of bone marrow transplant, with the presence of blood clots, endothelial damage, and end organ damage and death. Mortality is as high as 40% after one year of diagnosis, but in the most severe segment of the patient population, which often are children, mortality is as high as 80% after one year. So very severe condition. Very importantly, there's no medication available for this indication. Now, complement inhibition has demonstrated over the years to be potentially very effective in this thrombotic microangiopathy. As a matter of fact, Soliris has been used by physicians.
We have case studies and some publications, which together give us confidence that complement has an important role in this disease. For this reason, we started two phase III studies, one in adults, which is a placebo-controlled study, and a pediatric study ongoing as well with 40 patients. The endpoints are hard endpoints. We're looking at complete TMA response, measured as hematological response and renal response, as well as overall survival in these patient populations. The studies are well advanced in recruitment, and we do expect data readout in 2025. You can imagine, given the high number of this procedure and the fact there's no medicine available, we believe that Ultomiris can be a game changer in this indication, and most importantly, save lives of many children worldwide.
The second indication I would like to talk about, it's actually efforts in IgAN or IgA nephropathy, immunoglobulin A nephropathy. This is a disease that happens when basically your immune system produce abnormal IgA, which deposit in the kidneys, forming immune complexes. These immune complexes activate complement, which cause inflammation. Inflammation cause damage, chronic kidney disease, leading to dialysis, eventually the requirement of a renal transplant... There's 120,000 diagnosed patients in the U.S. with this condition, and as you can see, the outcome is quite poor. 60%-80% of high-risk patients experience kidney failure within 10 years. To provide you a clinical picture, the typical patient is, young man in his 20s. You get a diagnosis of IgA nephropathy. The disease is slowly progressing, and by the age of 40, you need dialysis or a renal transplant. So very severe condition.
The first line of intervention, as you can see here from the slide, it's really ACE and ARB, and also the use of Farxiga. You heard this morning very nicely how Farxiga is expanding in multiple indications, but Farxiga has a very important role here, and in fact, it's becoming part of the standard of care as the first-line intervention. There are also a number on the endothelin receptor antagonists as well, which are currently in development, and we believe they could have an important role as a first-line intervention as well. However, the disease is an immune-mediated disease, and as a clinical immunologist myself, I do believe that you need to tackle the underlying disease to be able to really slow progression to end-stage renal disease.
So complement inhibition can do that, has the potential to be a disease modifier, and we do expect disease modifiers in general to be positioned, as you can see, as a second line of therapy in the more severe segment, those with high proteinuria, measured at 0.75 gram per gram by UPCR. We have opportunity with two assets. Vemircopan is our Factor D inhibitor, second generation, and Ultomiris, our, of course, second-generation C5. Vemircopan is currently in phase II development, and Ultomiris is in development in phase III in this indication. Now, more importantly, you can see with the broad spectrum of assets that we have at AstraZeneca, we're really able to tackle the disease broadly from mild patients all the way to severe patients, and we are uniquely positioned to do that. I mentioned that complement has a very important role in disease.
Well, evidence comes both from preclinical data as well as clinical data. Here, I'm showing you the results of our Phase II studies with Ultomiris, the Sanctuary study, which was presented at the American Society of Nephrology last year. You can see that was the study with Ultomiris was a placebo-controlled study over 26 weeks. We saw a rapid, sustained, and complete complement inhibition very quickly in the study, which led to an improvement in proteinuria with a reduction of over 40%, which is currently best in class among complement inhibition. In addition to that, what is striking is the fast onset of action, which occur as quickly as 4 weeks and then is sustained over time.
We believe this is fast onset of action is really one of the key elements for differentiation in the class of disease modifiers because of the mechanism of action of complement and the immediate stop of the inflammation, which is causing damage. And this will set us apart as compared to the competition in this class of therapies. Of course, we also served stable GFR during the course of the studies by the small number, which is very promising for the final data readout. We're currently running a Phase III study, the iGAN study, which was initiated, and we do expect the data readout after 2025. As you can see, the study has 450 patients, and you can see the endpoint here.
We're looking at proteinuria at 3, week 34, basically 9 months, and eGFR at 2 years in the study. With that, I'll pass it over to Marc to continue discuss our efforts in renal transplant.
So I will take it from the left of this slide, and these are the... As you can see on the left of this slide, you have the chronic kidney disease that Gianluca has just presented to you, iGAN. What I will do now is to move what happens if you progress from this stage? And then basically, you have two solutions: either you go into dialysis or you go into, or you receive a renal transplant. And obviously, we all know that renal transplant is a much better clinical solution than dialysis in terms of long-term prognosis. However, as you all know, the availability of organ donated is well inferior to the people needing a transplant.
So basically, what we are going to focus with our complement products is to try and help in the transplant allergy world in two ways. At the top, you have the antibody-mediated rejection, so we're not going to intervene at the acute stage, but we plan to have a benefit on the chronic antibody-mediated, and we intend to use our silencer of C3 for that specific indication. The statistic at the top right, 12% of incidents, 12% of transplants get to this chronic AMR. And more importantly, once you get the AMR, 75% of these patients will lose their graft function within 5 years. So it's a very grim outlook. At the bottom, it's a totally different thing. We are trying to increase the success rate of the renal transplant and avoid the delayed graft function.
Basically, we are trying to accelerate the time to freedom from dialysis. When you receive a renal transplant, you need to be on a short-term dialysis, and hopefully, you will get out of this dialysis within days. What Ultomiris should be able to do is to help increase the to accelerate the relief from or the freedom from dialysis from the dialysis. So now if you and then you arrive at this if you do that, you can also indirectly do something else. You can improve the utilization rate of the the renal donated. Today, in the United States, 28% of the kidneys which are donated are not cannot be implanted within this window of opportunity.
So by delaying the window of opportunity, you can also improve the organ that are used, and therefore reduce the kidney waiting line, which is absolutely very large. I mean, we believe that 350,000 or 400,000 patients globally are in a waiting line for a kidney transplant. So if you can ameliorate the success of the transplant, and then these patients do not have to undergo a second transplant, but also accelerate the lengthen the duration under which the surgeon can transplant, then, you know, you are improving it on both sides. So we are doing some work on this. Our phase 3 is going to start for delayed graft function within 2024. Let me sum up now the complement section, if I can. Okay.
Okay, so basically to summarize, we have 3 products already approved in 4 indications, and we are pursuing 4 more assets in 6 separate indication. You can see several of them for Ultomiris, in the Ultomiris box, but we have also Vemircopan, our number 2, Factor D, as well as eanicopan, number 1. I mentioned the Silencer 2030 in chronic AMR. With this, I will go to the beyond the complement, which is the second avenue for us. So for us, beyond the complement means bone and endocrine rare disease, as well as amyloidosis. So let me first talk about hypophosphatasia. Hypophosphatasia is a disease caused by a deficiency in the enzyme alkaline phosphatase, and the cause of that deficiency is, you know, extreme impaired bone formation. In neonatal, it can be absolutely fatal.
You have X-rays of what's happening in Strensiq patients. Their bone are absolutely not formed, and in some neonatal cases, the rib of the child is nearly non-existent. So it's a terrific disease. Strensiq has been on the market since 2015. It has reached a blockbuster status in 2023. The product is progressing very well. As you can see on the left panel, a growth of 20% or 21%, so it's a very important product for this disease. However, the product has to be administered every day or every other day through a subcut injection. And what the researchers at Alexion have invented is to find another enzyme replacement, but a product that can be administered every two weeks.
So this is going to make a very large difference for the patients undergoing treatment. We expect that the population will be six times as large as that of Strensiq today. We have three clinical trials, which are conducted globally, and the data are anticipated post-2025. We have two pediatric studies, one switch, one naive, as well as one adolescent and adult comparative trial. And with this, Gianluca?
Thank you. I'm going to discuss about the new product in our pipeline, which I'm very excited about, which is eneboparatide. You heard earlier this year, we announced the plan to acquire Amolyt Pharma, which will give us eneboparatide, which is the best in-class therapy for hypoparathyroidism. Hypoparathyroidism is a hormone deficiency. It's a deficiency of the parathyroid hormone, which is basically responsible for the control of calcium level as well as phosphate in our blood. It's one of the more less rare, rare diseases. Many of these patients suffer from multiple symptoms, including muscle spasm, cardiac effects, and neurological effects as well. So the clinical priorities for this disease are normalizing the serum calcium level to be able to avoid all of the symptoms that I mentioned.
The second priority is about decreasing urinary calcium excretion, especially taking into account that about 50% of these patients have hypercalciuria. They develop calcinosis, which leads to chronic kidney disease. The third priority is to preserve the bone mineral density, preventing osteoporosis. Here again, you can see that the majority of the patients are women, and more than 50% of them are peri or post-menopausal, therefore, they are at risk of osteopenia. Here in the middle, you can see the very strong phase 2 data of this drug, demonstrating the stabilization of a calcium level during the entire treatment period, despite the decrease or complete elimination of supplement with calcium and vitamin D.
In addition, the phase 2 clinical study also demonstrated decreasing urinary calcium levels and the preservation of the bone mineral density, both by mild markers of bone mineral density and DXA scan. Now, I'm highlighting these two elements, so urinary calcium and bone mineral density, because these are the two elements for great differentiation as compared to the current competition, and that's why we believe that Eneboparatide is going to be a highly differentiated and potentially a blockbuster medication.
... One second on the, just before I forgot, I forgot to mention it earlier on. These little boxes at the top right, these represent the peak year sales on a known risk-adjusted basis. If, if you have, maybe some of you may not have noted, we have not on every page, but whenever possible, we try to provide some indication on the peak sales revenue.
Excellent. So following the phase two, the company started a phase three program, Calypso. The study rolled quicker than expected, and in fact, data readout now is expected for next year. And also, a couple of weeks ago, the company had breakthrough designation from the FDA, given the strength and the relevance of the phase two data that I mentioned. This comp, this product will strengthen our presence in rare endocrinology, also expanding from Strensiq physician call points. So it's a very nice synergy as well in terms of call points. And now, let me give you a few words about the amyloidosis franchise. You heard previously that we are focusing as a company with all amyloidosis, that really what is the, at the core of the disease is the deposition of amyloid fibril in the organs, systemically causing organ damage.
The heart is largely one of the main organ affected. So you see a lot of cardiovascular hospitalization in these patients, as well as high mortalities. Rate of mortalities can be very high as soon as one year after diagnosis. The other critical element of amyloidosis is a lack of diagnosis. You heard how there is a great opportunity to increase diagnostics in general, would represent an expansion of this very large franchise. So how are we tackling the disease at Alexion? We are focusing on the production of depleter antibodies. These antibodies, they bind to the amyloid fibrils. They recognize them specifically. They activate the immune system directly in the fibrils to be able to eliminate them from the organ, and therefore, rescue organ function. That's the whole idea behind depleting antibodies. We have developed two of them.
The first one is the ALXN2220, which is targeting the ATTR amyloidosis, the most prevalent form of amyloidosis, 114 patients diagnosed in U.S. and in Europe, and we currently recently issued a phase III study. The second antibody that we developed is anselamimab, targeting the second form of amyloidosis, which is the light chain amyloidosis or AL amyloidosis. Here, too, you see 28,000 patients diagnosed, and we completed enrollment in the phase III for this product. We discussed earlier the opportunity in the ATTR amyloidosis, but I would say it's pretty clear that by leveraging both the knowledge and expertise in CVRM, as well as in the rare disease unit, we're uniquely positioned to tackle the disease with multiple angles, and really treat the broader spectrum of the patient population.
You heard previously about silencers with Wainua, which block the TTR synthesis directly in the liver. We're also developing a stabilizer in Japan, the Acoramidis. It's a super stabilizer, which had the opportunity to stabilize the tetramers, therefore reduce the accumulation of amyloid in the fibril as well. But most importantly, we are focusing on the depleter approach, which bind to the misfolded TTR protein, removing the toxic fibrils, and therefore restoring organ function. As you can see, because the depleter has the opportunity to restore the organ function, we are fundamentally focused on a more severe patient population. So on the right-hand side, you see with the Alexion 2220, we are targeting moderate to severe patient, taking the NYHA classification.
This corresponds to a part of the class two, class three, and class four, while silencer and stabilizer are focused on NYHA class one, two, and three. But overall, as you can see, we can. We have the opportunity to treat the broader spectrum of the patient populations. Now, let's hear a little bit more about the mechanism of action of depletion of the Alexion 2220. I'm going to show you a video. What I found very exciting about this video is that we use human samples, bio samples from patients with the CM amyloidosis, exposed directly with our antibody. So you can actually see the antibody in action.
ATTR-CM is a systemic disease caused by the breakdown and deposition of a protein called transthyretin or TTR. These misfolded proteins, called amyloid fibrils, can lead to cardiomyopathy, heart failure, and death. Macrophages are immune cells specialized in removing bacteria, viruses, and dead cell debris, but do not independently recognize amyloid fibrils as foreign. ALXN-2220 is an investigational antibody, and in presence of ALXN-2220, macrophages recognize amyloid deposits and remove them by a process called phagocytosis. By depleting amyloid buildup from the heart, we aim to restore cardiac function. ALXN-2220 is being tested in late-stage clinical trials for the treatment of ATTR cardiomyopathy as an add-on to standard of care.
I have to say I was very excited to see for the first time this macrophages chewing up the amyloid deposition. So as a scientist, it's quite revealing in a way, so very exciting. And as a matter of fact, we do believe that the ATTR product, the Alexion 2220, has the potential to reverse the course of the disease. This was demonstrated already in a phase 1b study, which was a small study, 40 patients, placebo-controlled, published in the New England Journal of Medicine last year, and also presented at the European Society of Cardiology. And the study demonstrated a dramatic reduction on the bulk of amyloid in the tissues via imaging using MRI and scintigraphy.
What you see here is an illustrative example of one patient, and I think, the image says it all. You can see how there was a dramatic reduction of amyloid deposition from the heart already at four months with almost normalization, and this continued over a 12-month treatment period. Importantly, we also saw a reduction of cardiac biomarkers, including NT-proBNP and troponin T, demonstrating improvement of cardiac function, and these biomarkers are also directly related to cardiac outcome, which is very important. The phase 1b was strong enough to that we negotiated with regulators globally to go directly to a phase 3 program. This was started this year. It's a 1,000 patient program with a 2-to-1 randomization and again, focusing on hard endpoints, including all-cause mortality and cardiovascular events. I look forward for the result for this program.
Then finally, I would like to conclude by just saying a few words on our AL amyloidosis program. I mean, this is also quite exciting and quite novel. The AL amyloidosis is caused by defective plasma cells that produce very high level of light chains, depositing in the tissues, causing amyloid depositions, and of course, organ damage. In this specific case, the two organs mostly damaged are the kidneys and the heart, leading eventually to death. In fact, the median overall survival for newly diagnosed stage three B patients, it's only nine months, which is equal to quite severe cancers, as you can see. The approach here is pretty much the same in terms of mechanism of action. So it's a depleter antibody. They recognize specifically the fibrils in the tissue, eliminate them, and therefore improve organ function.
Our phase 2 study demonstrated improvement in cardiac function as early as 10 weeks, and in renal function as early as 14 weeks, giving us confidence. We're now running a phase 3 program. Actually, there are two studies, one focusing on the 3A patients, Mayo 3A, so the moderate segment of the patient population, and there's a study focusing on the severe segment, which is the phase 3B, overall encompassing about 40% of the patient population with the AL amyloidosis. Here again, hard endpoints, all-cause mortality, and cardiovascular hospitalization, and we do anticipate a readout next year. With that, I'll hand it over to Marc to discuss briefly our efforts in gene therapy and for the closing remarks.
Thank you. So I would not, I needed to spend maybe one slide on the day after tomorrow, and for us, the day after tomorrow is genomic medicine. As you know, 80% of the rare disease have genetic cause, either inherited or acquired mutation. So what we have done until now is to assemble together with our organic capabilities. We have assembled capabilities from other companies in research or acquired some portfolio, in particular from Pfizer. And we are working on both on viral and non-viral delivery, as well as gene therapy and gene editing. We have a portfolio of more than 10 projects, preclinical. Some of them are reaching clinical in the year 2024, and we expect to advance two INDs per year to 2030.
These products will not, you know, will start generating revenues towards the year 2030. Then my last slide of conclusion, like, we have said earlier on, we have given you some vignette of the size of every product, but we have now grouped them in some buckets above $5 billion. Clearly, Ultomiris is going to be more than a $5 billion drug. Then we have seen the enzyme replacement, the new enzyme replacement, as well as the product that Gianluca just described, Alexion 2220 in the ATTR Cardiomyopathy. So in the category 3-5, and then in the 1-3 category, we have Anselamimab and Eneboparatide, as well as Gefurulimab or third generation.
So I think we are well positioned to continue in our franchise, and we look forward to continuing also pioneering new indication for the complement and outside the complement. Thank you. So this open a Q&A, and I will invite two other of my colleagues on stage. Yes? We need a microphone, I think.
Thanks. Sachin Jain, Bank of America. First one's commercial and second pipeline. So firstly, on PNH, could you just talk to the commercial impact that you've seen from Novartis' Factor B launch and how you're using your Factor D as rebuttal? And then the second question is on the TTR depleter. Any points of differentiation that you'd flag versus the Novo Nordisk Prothena asset? And then in the introduction, Pascal mentioned combination with the silencer. Is that in progress? Do you have any data there? Thank you.
... Mm-hmm, the first one, and Gianluca, maybe you can take second and third?
Yep, very happy to. So thank you for the question. So as you've pointed out, Novartis did launch a product at the beginning of this year. We also launched Voydeya, which we only briefly touched on, on the slides. And the opportunity with Voydeya is to be able to add on to Ultomiris in patients that have clinically relevant EVH, which we think is probably about 10%-20% of patients. And so far, we've managed to launch Voydeya in the US, we've launched it in Japan, and we're just in the process of launching in Europe. So even though it's very early days for Novartis with Iptacopan, and also early days for us, we're seeing some initial usage, as expected, probably in the 10%-20% range.
We do believe that this provides an opportunity for patients who may suffer from the EVH without having to come off Ultomiris. And Ultomiris in PNH, obviously, with its many, many years of experience, I think physicians are truly believing it's the right way to control patients on the long term without taking patients off and having to switch to another medication. So, so far, early days, but we believe the feedback we've had on Voydeya helps us to understand the place that Iptacopan could play. And at this stage, you know, very much continuing to talk about the opportunity for Ultomiris to treat patients on the long term.
Gianluca?
You asked the question about Novo Nordisk. What I can say is that obviously, it's very early days. We did a lot of efforts demonstrating the effectiveness of the mechanism of action on the drug. So the element that you saw, the binding of the phagocytosis in vitro, all show very high confidence on the mechanism of action and ability to bind and also to eliminate the deposition of amyloid. The effect in the data was very strong despite the small size of the study with 40 patients. It's early days to be able to make a comparison directly in Novo Nordisk. What I can say is that there's two elements. Number one, we are performing one of the largest studies in cardiovascular, in ATTR amyloidosis as of to date, which shows you the enormous effort of the company around ATTR.
The study is 1,000 patients, and it's targeting moderate to severe patient, which is 50% of the patients targeted by silencers and stabilizers, including, in addition, the more serious segment of the patient population. So the wealth of data that the study will provide will be certainly unique, and we'll be able to potentially differentiate. In addition to that, we're also thinking about going early in line of therapy. So we're looking at milder patients. We're looking into plans into doing that because we believe that the uniqueness of the mechanism of action is you are taking out the deposit from the tissues. You take out the garbage, basically, and at the same time, with stabilizers and silencers, you inhibit the deposition of that into the tissues. So we'll be uniquely positioned because our study is large enough.
We collect data on top of Stabilizer and Soliris and give an answer to the role of the feeder. We're also performing an extension of the phase 1 study, where we are going to analyze lower dose of the antibody or potential antibody holidays as well, which should give us a sense if the antibody, the feeder should be given chronically or depending on the need of patient, which is very unique as an approach. I would say, finally, you saw the broad spectrum of the product that we have at AstraZeneca. I think we're uniquely positioned also to potentially combine this medication, which is going to set up as the probably the strongest player in the ATTR field, and I'm very confident about that.
Maybe just in short and in summary, the trial that we are doing is as an add-on to standard of care. Standard of care being defined as Stabilizer today, tomorrow it will also be Stabilizer and Soliris. So we'll have data from that very large trial coming our way. And we are also thinking of other possible design for a combination. And so maybe I get to the second question. Yes? Over there.
Sorry. Thank you very much.
Thank you. Simon Baker from Redburn Atlantic. Two, if I may, please. Firstly, could you give us your thoughts on how the myasthenia gravis market is evolving relative to your expectations a couple of years ago, given the number of new entrants we've seen there? And then secondly, going on to the comments you made about gene therapy, Marc, I think you said you, you're exploring both viral and non-viral delivery methodologies. I wonder if you could elaborate on some of the non-viral approaches that you're trying. Thanks so much.
Okay. So I think we provided some view of the evolution of the market of myasthenia gravis. And we see this very rapid increase of the branded medicine hours and that of competitors in the market of myasthenia gravis, which was until now, basically treated with steroids and, you know, variety of unapproved immunosuppressant in that indication. So we see this... Now, the guidelines are being published around the world by different geographies, and they all insist on having, you know, properly approved medicine with demonstration of the control of symptoms, and also attempting to reduce the steroid usage.
So these are now, you know, these guidelines are being introduced all around the world and becoming clearer and clearer, and we do expect branded medicine to increase, and we mentioned a figure of about 80% by 2034. So we see this continued growth of the neuro-- of the myasthenia gravis usage for our products as well as that of competitors. Your second question maybe is same, maybe you can help answer this?
Yeah, so maybe I can start by saying that, you know, gene therapy as a technology clearly is a strategic fit, as you heard from Pascal this morning. It is an effort on our part to obviously look for innovation in the form of new technologies that in particular transform patient outcomes. And clearly, gene therapy represents one such technology, and that it addresses the primary underlying basis of genetic diseases that, as you heard from Mark, represents 80% of all rare diseases. So it's a very good fit for what we want to do to apply this really very exciting technology.
The last several months, maybe a few years, what we've done is actually develop a portfolio of programs that reflects the investments that started actually originally in AstraZeneca some years ago, but obviously augmented over the last 18 months by acquisitions and partnerships, such that today, as Mark indicated, we have up to around 10-12 programs are active, that are based primarily on the use of viral-based systems to address those disease indications. Maybe just quickly to say that those areas that we are addressing are focused on rare neurological as well as rare myopathies, which are therapeutic areas that are aligned with our strategic interest that you heard this afternoon.
And the partnership and acquisitions that we made also brought in significant talent, as well as know-how, and technologies that allow to apply the AAV vectors, in this case, the viral-based system that we're using for a number of these monogenic diseases. But we've also been exploring the potential of gene editing, and the preferred route of delivery of the editing machinery is typically in the context of a lipid nanoparticle or a synthetic or non-viral-based approach for that particular technology that we're trying to address. So that's the basis for the virus and non-viral approaches that we talk about.
Yeah. Thank you very much. Yes, over there?
Thank you very much. Thank you. Peter Welford at Jefferies. Two questions. Firstly, just on your aspirations to grow the rare disease business via deals. We obviously saw you do a deal for Eneboparatide this year. Is your target profile very much the larger genetic diseases? I mean, we've seen a lot of these programs have multi-billion potential, but there are thousands of rare diseases still untapped. But you know, is your focus very much those larger diseases with that big potential? And I guess that goes on to then the gene therapy, whereby in gene therapy, are you also, again, targeting those areas that are relatively large gene therapy opportunities, rather than perhaps get approval of the platform and then apply that to multiple, I guess, indications, monogenic diseases?
How do you think about gene therapy in rare diseases? Are you willing to be a second or third player in a disease, or do you think in this area, first, second, or otherwise, too late for the game?
Yeah. So let me answer this second question first, whether in the gene therapy we want to compete by being the first, second, or the third. Now, obviously, it's easier to compete in the first position, because if your product is already well, you know, structured and you have a good tissue distribution, you will certainly capture a lot of the prevalent population. If you come up later on, number three, number four, whatever, you will only get the incident, so to speak. So one has to be trading off the speed or the timing of launch versus the differentiation of your own construct. And that's obviously a balance that we need to look at for each and every indication or every product we construct. So there's not, unfortunately, there's no simple answer on that.
You need to see whether you can differentiate when another gene therapy product has been introduced, but it's not always known in advance.
But maybe I can add one point to Mark. I think, though, that the, being a little bit later in the gene therapy game could be an advantage for us. There's a number of indication where gene therapy first generation is doing the, what it's supposed to do, but not necessarily clinically satisfying the 100% demand. Coming as a second generation or third generation, more advanced technology could be a big advantage. At Alexion, we're very close to patients and patients' communities, and there are several example of, diseases where the gene therapy first generation is not optimal, and the capture has not been maximal. So the incidence that, that Mark mentioned is not met yet.
For example, the hemophilia, and there are other example of diseases where a treatment exists, and therefore, patients would rather expect for the second generation rather than the first generation. So I think as Mark said, it's a, it's a careful combination of analyzing each of the disease, what can be done, but as long as you can be transformational in the outcome, that's what it really matters. And I think we should come out from our pipeline that all of our product has been transformational, and we focus on transformational product, no matter the incidence and the prevalence of the disease.
Yeah, absolutely. Building on that transformational comment to your first question about the business development and sort of opportunities for us, we're looking for the unmet need for the patients that are not well served. So when we are looking at business development options, we're looking to really find something that's unique and differentiated. Clearly, if it's over $1 billion, that's great, but we're also looking at other options too. And the important thing is can we do good there? Are there good adjacencies with the other work that we're doing? And so Eneboparatide is a great example of where there are some synergies and maybe more to be created in the future with Strensiq and our 1850 molecule coming through down the line.
So it's a great confluence of a massive unmet need, a great profile, and also really good synergies. We continue to look for things like that, almost regardless of the size.
Yeah.
A question over there? Yes.
Hi, Gonzalo Artiach from Danske Bank. Thank you for taking my questions. I have one on Anselamimab and the comparison of this product with Prothena's Birtamimab. They are testing Prothena's Birtamimab in stage four of the disease. But beyond that, is there any competitive edge where you believe that Anselamimab could beat, for example, let's say, in mechanism of action or... Yeah.
So maybe I'll chime in with that one. So first of all, there is in vitro preclinical data showing that the affinity of the antibody, Anselamimab, is much higher than the Prothena antibody that you're referring to. So we do believe that the effect will be higher in terms of binding directly to the site. The second differentiation is the type of light chains that the antibody is able to recognize. Anselamimab has a much broader spectrum of light chains, including both lambda and kappa chains, which is not the case for the competition. Also, there is a third element of differentiation, again, based on in vitro preclinical data, that we demonstrated that our antibodies basically is able to bind to the amyloid through imaging, following directly into patients, which has never been demonstrated for the competition.
In addition to that, if you look at the clinical studies, as I mentioned, we have two large clinical studies. One is focused on the entire Mayo 3A population, and the second one is focused on the 3B population. Taken together, these are 40% of the AL amyloidosis population. And I have to say, taken together, the two studies represent 400 patients in this disease, which is by far the largest study ever performed in AL amyloidosis, which is actually quite impressive, and we recruited both of the studies now completely. So the competitor is only focused on a segment on the phase 3A population based on a post-hoc analysis they had in agreement with the FDA. So overall, if we do see an effect on the broader population, we believe we're gonna have a much more competitive product.
Thanks.
Thank you. Yes, over there. At the back.
Thank you, Marc. It's Matthew Weston at UBS. You flagged the headwind of Soliris, which is coming. Clearly, the main defense is to switch patients to Ultomiris, and that's progressing well. But I'd be very interested in, of the legacy Soliris revenue that you are gonna be left with, can you help investors understand the speed of erosion that you're anticipating within your numbers? Do you think it'll be very gradual? Do you think there'll be some levels of stepwise reduction over time?
Okay, so let me try to answer that one. So first of all, as we mentioned in the indication where we have both in, in the portfolio for the indication where we have dual indications, basically, the very rapid conversion, this is usually 12-18 months, and you reach about 80%. So obviously, 20% remain on Soliris overall. So this would be a population that could be vulnerable to biosimilars, but it is not proven or given that this patient will want to move to a biosimilar. So we need to see that. We already have examples of biosimilar approval in Europe, and there we see a gradual, a very slow, gradual introduction of biosimilars in Europe. So they do enter the market, but their, the proportion of patient they capture is, for the time being, very limited.
Yeah.
So that's the only data that we can, you know, derive or view from. And the progression is, for the time being, slow. Yes?
Thank you. Matthias Häggblom, Handelsbanken. 2 questions, please. So with 10 phase 3 assets at Alexion, I assume most of them remains underappreciated in your view. So historically, does data suggest success rate within rare disease is higher or lower than the company average? And then secondly, maybe for Aradhana, when a company allocates capital through business development, is there a preferred ranking between rare disease, biopharm, or oncology, or do they compete on the same merits? Thank you.
So I think your question was: Is there a preferred child that gets more dollars at the end of the day for business development? I don't know who's asking that question, but the answer is no. And actually, I will cover some of our, how we allocate resources within the company, not just for external opportunities, but also within our own pipeline, because obviously, our R&D teams you've met today are way more productive than we have money for. So, that's always. There's always a constraint.
Very good. Can you remind me your first question?
Success rates...
I think it's a difficult question. I think the success rate obviously depends if the, you know, if you have precedented data or not, or if you can extrapolate from one, you know, study to the other. Even if you use the same product, I don't know, complement inhibitor, for instance, if you are pioneering absolutely new usage, you need to demonstrate it with a new clinical design. Often, you need to invent the endpoint. You need to get it validated and accepted by authorities. So, I'm not sure it's... We are absolutely certain that the complement works. Sometimes it's not that easy to demonstrate in a relatively limited population. But I wouldn't say the rare dis-- I mean, probably in gene therapy-...
Because you know exactly the cause of the disease, and if you have the construct that answer that question, you can probably improve your success rate. Now, there you have other issues to solve, like safety, and whether the capsid, if you use antiviral, you know, delivers to the right tissue. So there are other obstacle, but once you have mastered this assembly, I would say, if you know the cause of the disease, you probably can have higher success rate than normal pharmaceuticals. But it's not a simple question, unfortunately. We are reaching the end of the session, and I want to thank you for, first of all, your interest in the world of rare disease. Thank you very much.
With more than 40 years' experience in developing cancer treatments, AstraZeneca is leading a revolution in oncology. Following the science to understand cancer and all its complexities, to discover, develop, and deliver life-changing medicines to patients. We make medicines that matter. With 11 approved cancer medicines already available, including Tagrisso, Lynparza, Imfinzi, Imjudo, Calquence, Enhertu, and now Truqap. We leverage our scale to lead in areas of high unmet need, such as lung, breast, and gastrointestinal cancers, and we are transforming patient care through early detection and precision diagnostics. Our broad and deep pipeline includes pioneering platforms such as antibody drug conjugates, next generation immuno-oncology, radioconjugates, epigenetics, and cell therapies. By attacking cancer from multiple angles, treating earlier and smarter, and advancing powerful combinations, we strive to transform the lives of patients living with cancer.
It's our vision to redefine cancer care and one day eliminate cancer as a cause of death.
Welcome, everybody. As you've heard, our goal is to eliminate cancer as a cause of death. What we want to share with you this afternoon is how we are making tangible progress towards that goal to improve survival rates by 2030 and beyond, across a range of different cancers. Despite the improvements that there have been in cancer over several decades, there remains a significant unmet need. This slide summarizes the new cases of cancer in the G7 and China in 2022, and also the five-year survival rate in the first-line metastatic setting. You can see there is considerable room for improvement. Just look at the numbers for lung cancer, for gastric cancer, and for acute myeloid leukemia.
But what gives me optimism that we can indeed substantially improve the survival outcomes is a number of critical trends that are happening across cancer discovery and development, which leads me to believe that we're in a golden age for cancer discovery and development. So first of all, with the optimization of the technologies around Antibody Drug Conjugates, we can see that we can pretty improve and replace backbone chemotherapy. And now with the advent of Radioconjugates, we're seeing that potential as well to improve another core backbone of treatment, which is radiotherapy. The second is that we can improve on the paradigm change that has been the immune checkpoint inhibition revolution, and the next wave of agents in this space can be targeted to better segment the patient population and improve on that innovation.
The third thing is that there's new ways of addressing and bringing in the immune system to fight cancer. With T-cell engagers that can specifically activate T-cells within the cancer, and cell therapies that are genetically engineered to deliver very active, effective cell killing of T-cells, and also genetic engineering to overcome the immunosuppressive microenvironment. But one key piece that you've already heard as a theme across the sessions today is the power of combinations. We're now seeing data about how we can put together ADCs, radioconjugates, and these next generation IO combinations into really effective, transformative combinations. And then finally, we need to move these regimens into the earlier stages of cancer, where there's the greatest potential for long-term survival and the potential for cure for some patients.
So we have very deliberately built our portfolio in oncology to create the toolbox that you see illustrated on what we call the color wheel on the left-hand side of this slide. Multiple different mechanisms that can combine together effectively to deliver transformative regimens. We've been investing in technologies to improve the early diagnosis of cancer and partner with companies like Grail, like Guardant Health, in this space, to help with the early diagnosis of cancer and help create novel trial designs that can help move our agents into this setting at an earlier point. We can also use this kind of technology to monitor patients and use adaptive treatment regimens to improve outcomes. We've embedded data science and AI throughout our discovery and development programs to improve our timelines and to improve our technical success rates.
We've invested in computational pathology, which I think is going to be a really important part of treating the right patients with our portfolio of antibody drug conjugates. We're embedding digital health technologies in partnership with Evinova across our portfolio, to help support patients and investigators to give them the best care, to identify adverse events at an early point, to document them, and to intervene so we can make a bigger difference. What is really transformative is putting all of these together as an integrated strategy, and that's what we think we can be different and how we can be differentiated from the competition. Let me just demonstrate here on this slide, an example of how you create what we call these transformative regimens. Current standard of care uses combination chemotherapy or radiotherapy together with surgery to debulk cancers.
That debulking element of cancer treatment will remain important, and we can use antibody-drug conjugates, radioconjugates, and our IO bispecifics together to create effective debulking therapy. Particularly effective if we use it into the early stages or the neoadjuvant setting of treatment. We also know that if we use, for example, the example that's been in hematologic malignancies for some time, where patients are treated with bone marrow transplant when they've had a setting of minimal residual disease or a complete response, that is the best way to create long-term survival benefit. That analogy is applicable also to solid tumors, and this is the space which, if we can identify these patients with minimal residual disease, we can use our T-cell engagers and CAR-Ts and give those therapies the best chance of working in those earlier stage.
This movement will happen over time, but this is part of our core strategy. There are other combinations. For example, our PARP inhibitors will combine well with radioconjugates, and with the ADCs in this setting to help improve the transformative regimens. Antibody-drug conjugates are a core part of this vision for transforming cancer care, and we are leading the ADC revolution. You can see we've just started when you look at the potential on the left-hand side of the number of patients that could be treated with ADCs at peak across a range of different tumor types. We started with a strong foundation, with partnership with our colleagues at Daiichi Sankyo, for our leading ADCs with Enhertu and Dato-DXd. But we've used the time that we gained from that to build an impressive portfolio of internal ADCs.
We've got six clinical-stage internal ADCs now, and others that are coming through into the clinic. We're also now developing key combinations with the immunotherapy agents that we have in our portfolio and our DNA damage response portfolio. Use an example of Enhertu as an example of this journey that I'm talking about. We started with Enhertu in the space where an ADC was already approved, with the. And we improved upon that because of the next-generation technology we have in our new ADCs, with better linkers and better warheads. What we showed in the HER2 high space in breast cancer is a significant improvement in progression-free survival and overall survival with the DESTINY Breast-03 data.
We then moved into a space where the current generation of ADCs could not go, that were directed against, HER2, with the DESTINY Breast-04 data in the lower HER2 expressing breast cancer setting, in a second-line-plus, patient population, third-line-plus patient population with the DESTINY Breast-04. And then, most recently, we've got paradigm-changing approval with the pan-tumor, tumor-agnostic label based on the DESTINY Pan-Tumor-02 data, again, in HER2 high-expressing tumors with a range of different tumor types. This shows that we can replace backbone chemotherapy in multiple settings and also the older generation of ADCs. With our second ADC, Dato-DXd, we've also got two positive pivotal Phase III trials in non-small cell lung cancer and breast cancer, also showing improvement in terms of efficacy and safety versus standard of care chemotherapy in these difficult-to-treat settings.
What I think we're going to need in order to further optimize our ADCs is identify the right patient populations, and this is a place where you're going to hear more about how we're doing that, not just for Dato-DXd, but across our portfolio. So the next part of our strategy is how we improve on the paradigm change that has been immune checkpoint inhibition in cancer, and we're doing that with our bispecific portfolio. So Rilvegostomig is a PD-1 TIGIT bispecific antibody. It's designed to improve on the activity of PD-1 or PD-L1 agents alone in the patient population are already sensitive to immune checkpoint inhibition. This tends to be at the higher levels of PD-L1 expression, for example, in lung cancer, or in the very PD-1-sensitive tumor types. Volrustomig is our PD-1 CTLA-4 bispecific. We know that CTLA-4 inhibition can improve long-term survival.
It can improve that tail on the survival curves, but comes with a toxicity profile, which has limited the use currently of anti-CTLA-4 antibodies. This molecule was designed to minimize those toxicities and deliver full inhibition of PD-1 at levels of CTLA-4 inhibition, which go beyond what is currently available with either tremelimumab or ipilimumab. By doing this together, we're going to target the patient population where CTLA-4 inhibition can add the most benefit, for example, in the lower PD-L1-expressing areas of lung cancer or in CTLA-4-sensitive tumor types. And this is what I mean about better segmentation and patient selection of the next generation of IO agents. So let's just now see some of the clinical data that we're starting to see, looking at the combination of our ADCs and IO agents.
So we're gonna show you the example with the data that we've got with Dato-DXd together with Imfinzi, starting with the BEGONIA study in triple-negative breast cancer, first-line metastatic disease. This has delivered an unprecedented 79% response rate and nearly 14 months of median progression-free survival in a patient population where this had been the most difficult to treat area of breast cancer. We've also seen that same combination deliver impressive response rates in lung cancer, in first-line lung cancer. And one of the advantages of Dato-DXd is that because it has a stable linker, it produces lower bone marrow toxicity, and therefore you can combine it with platinum. And the triplet combination of Dato-DXd, Imfinzi, and platinum produces this impressive 77% response rate and a really good trend to improvement in progression-free survival.
What we've now done is we've taken this combination, we've moved it into the early-stage setting, where the potential for cure is highest. We have exciting data emerging in the neoadjuvant treatments of non-small cell lung cancer from the NeoCOAST-2 study, and also in breast cancer in the neoadjuvant setting for patients with TNBC and HR-positive, HER2-negative breast cancer in the I-SPY 2 trial. Those data will be presented at ASCO, and the data for NeoCOAST-2 will be presented in an upcoming congress later this year.
So I'll go back again and say we have very deliberately built our portfolio to enable the potential for this, these sets of combinations, and you can see that we have the portfolio that we need to lead in these ADCs plus IO combinations, and we're taking this into a number of different settings, not just lung cancer and breast cancers I've shown you, but gastric cancer, bladder cancer, and endometrial cancer with the range of agents that we have. And you'll hear more about this in the subsequent slides. And now I'm gonna hand over to David, who's going to talk to you about how we take this strategy for improving the outcomes of patients and actually deliver it to patients. David?
Thanks, Susan. I appreciate it very much. So Susan's walked through how we imagine collectively the treatment of cancer in 2030, and I think that you can see that there's a convergence of science and data and technology that's giving rise to this optimism that we have, that we can, as Susan pointed out on the previous slide, begin to bend survival curves. But indeed, the value of that is only real if we're able to deliver that in the real world. If at a postal code level, we're able to make sure that practice change is taking place. And so we've really worked intentionally on having every bit as differentiated a commercial strategy as we do the work that we have in R&D and the R&D strategy.
I'd like to put forth that the three elements that you see here are all very much intentional and differentiated in terms of how, as the Oncology Business Unit, we are driving a sustainable and differentiated strategy. Now, first, if we talk on the leftmost panel, really working to build transformative brands and medicines that matter. Now, indeed, all companies that are working within the space are focused in on building medicines that matter and transformative brands. But what I would offer is that to be able to have four or five multi-blockbusters sitting on this list is absolutely differentiated and unique, and I'll talk a little bit more about the work that we've done to get there.
But with Tagrisso, Imfinzi, Calquence, Enhertu, all of these multi-blockbusters, Lynparza, that will continue to drive growth through the 2030 period, and of course, Zoladex still remaining very relevant across the globe for prostate and breast cancer, and then Truqap, the latest arrival, which we've got multi-blockbuster expectations for. As you start to move to the middle panel, we start to get into places where I do think that AstraZeneca is uniquely owning the opportunity for scale and leadership within the tumor types that we're playing in and the tumor types that we're investing in. And that tumor type leadership is important, not only because it creates scale that we can leverage to launch new medicines, to get more rapidly up uptake curves.
That scale helps us in clinical trials and the operations that we do there, but it also allows us to have a different type of conversation with customers on how we want to be thinking about transforming the way in which they go through differential diagnosis, how they then think about that differential diagnosis, resulting in the choice of treatments that they want to be able to make. And what you can see is that already with the work that we've done in lung cancer, and we've talked about an ambition by 2030 of 1 in 2 patients being treated with an oncology medicine or being treated with an AstraZeneca medicine, and we think that we're well on our way to being able to accomplish that.
We add to that scale in breast, GI, Gyn, and what I'd really like for you also to listen to today is the scale that we're building within hematology and the work that we're doing there, because I think that it's something that's very much underappreciated. Finally, and where I do think that we're probably the most differentiated from a commercial standpoint relative to what you see others working on, is the effort that we're making to drive not just of our medicines, which of course, is something that we're focused in on. But how do we think about outcomes for patients and expand to thinking upstream of the decision to use our medicines and also downstream? Upstream, early detection, precision diagnosis. Obviously, then, of course, ensuring guidelines have been changed and reflect actually the best evidence-supported care. And then lastly, how we think about the patient experience.
That is adherence, compliance, side effect management. The work that we've done to build out capabilities around sales, marketing, medical, the access work, also what we're doing in commercial diagnostics and within commercial digital, is key to being able to deliver this. If you go to the next slide, Susan, what we can do is we can bring this to life. So it's not just a theoretical example. If we take a look at lung cancer here, and we look at the work that we've done in order to establish and build and transform and create a new standard of care in each of these areas, I think that it's really key and brings to life some of the core elements in terms of changing and transforming the delivery of care that had to take place in order for success to happen.
Now, obviously, you're very familiar, each of you, with the work that we've done within metastatic non-small cell lung cancer. And with FLAURA, we've established a market share of nearly three in four patients being treated with Tagrisso in this setting over the period of time that we've been working within this. But in order to accomplish that, we actually had to drive EGFR treatment rates from the 65%-70% rate that they were at before to even higher to the 80% that they're at now. Now, that may seem like no small feat, but those are actually very hard-earned yards. And we got there by establishing T790M prior to that as relevant in the treatment algorithm.
Our experience and expertise in establishing BRCA, HRD, T790M, PD-L1, all of these different biomarkers should give confidence that any time we bring a precision medicine companion diagnostic together with the work that we're doing, or we'll talk more, and Matt will talk more about QCS, that we've got the capabilities to be able to deliver that. With unresectable non-small cell lung cancer, so in the Pacific setting, again, we've established Pacific, two in three patients being treated with Imfinzi, the only PD-1, PD-L1 that's playing within this space. But it was non-trivial to be able to drive and increase the chemoradiotherapy rates that are happening for these particular patients. Nontrivial because it was about bringing together radiology, surgery, medical oncology, nurses, pathology, all together in the multidisciplinary teams to drive this work. We've established the ability to be able to do that.
That serves us well as we have conversations on ADRIATIC in the future. It serves us well as we move into LAURA for the future. We understand how to work together across these multidisciplinary teams, which is highly relevant as we think about what it takes to drive standard of care. Lastly, in the early setting with resectable non-small cell lung cancer, again, here in the U.S., about two in three patients being treated with Tagrisso in this stage 1B through 3A resectable patient population. Here, one of the biggest drivers that we had to change was not so much the decision to treat with Tagrisso, but the decision to use adjuvant treatment at all, breaking a belief that adjuvant treatment was unnecessary, which was actually a belief that was driven by kind of some of the lukewarm efficacy data that you saw with chemotherapy alone.
Each of these shows how within lung cancer, together, we've built scale, in lung cancer we've built relationships. We've done this across all parts of the globe. It allows us to focus in on lung cancer early detection. It allows us to build supply and capacity for companion diagnostics and assays in lung cancer as appropriate, and it sets the stage for what we've got coming next. Pascal talked about Laura. We know that we've got Adriatic that's coming in. We have AG and we have B31. We have over 10 phase 3 studies on the horizon. We've established, and I believe, the right to win with those particular studies that are coming through based upon the work that we've done. Susan, if you go to the next slide.
And so if there's one single slide that I think is really kind of the most important single thesis for oncology, that brings it all together, it's this. We all know that we're an $18 billion business in 2023. Of course, we've got IRA impact, and you heard us make comments in first quarter, or me specifically make a comment, that we are starting to see some signs, too early to quantify, of lower abandonment rates and improved access as affordability is improved. This is a good thing. Obviously, it comes with needing to pay the 20% for the catastrophic liability. And there's loss of exclusivity for Lynparza that'll come in the 2030 period.
But if you look to the right, the existing portfolio with 5 assets, all of which have considerable growth still remaining in the clinical development plans that are associated with those, and then 8 new NMEs, or really I should say 7 plus 1 basket of the AZ ADCs. 7 new ADCs, or 7 new NMEs, excuse me, within here, each of which we see as having substantial growth opportunity. You can see in here, there's bispecifics, there's hematology assets, there's antibody drug conjugates, there's targeted therapies, all of the areas that Susan has spoken to. And so if you look at what's really underpinning the thesis for why we believe we can win in oncology, it's sustained leadership in key scientific platforms that are resulting in transformative medicines: ADCs, radioconjugates, the bispecifics, cell therapy, T cell engagers. There's a broad portfolio that's also come out of that.
Susan talked about this. You'll hear more, and you should listen more for what are the unique combination opportunities? How do we think about the potential for precision medicine to really exploit this? We have a global differentiated commercial model, which hopefully I brought into the fold so that you could really appreciate and see. We've got multi-blockbuster medicines in hand with more that we are expecting. If you take a look at this, we really do believe that while obviously everything is not going to be able to be realized to its full potential, I do think that we've got the opportunity to contribute very meaningfully to the $80 billion that Pascal laid out at the beginning of today, and that's across both solid tumor and hematology. Next slide, Susan.
One of the key reasons to believe that we'd like to highlight that sits behind this, and this is largely, some company analysis together with you can see the sources that we've looked at here, but we believe that there's very much a correlation between investment in R&D and oncology and success commercially within oncology. This is looking across the top eight players. The lines that you see here represent the number of patients in phase three studies. Certainly, in the solid tumor world, we think this is an accurate and good way of taking a look at surrogates for success in hematology.
Perhaps it's a little bit less of an accurate surrogate, but what you can see is during the period of time, from 2010 through till 2022, we've been steadily increasing our investment in oncology, as measured by the number of patients in phase IIIs, and I think that you can certainly see that our revenues have gone along with that. We will continue to go in that direction. While what we observe is that the level is leveling out for other competitors within the space, we think that this is a good sign for the opportunity for us to succeed going forward. One more slide. Then, of course, we really have the opportunity to be able to see as a proof point, the news flow that's coming through. Just a couple of things to point out. We said that we were going to go early...
ADRIATIC and LAURA, just within this year, examples of going early, and of course, we've had others along the way. We've said that we will go with combinations. We've got GEMINI, we've got the ARTEMIDE studies that are coming through, but really, GEMINI and the Volrustomig studies that are going to go through, that will demonstrate that we've said what we're going to be doing on this. We've said that we will go with bispecifics. We've said ADCs. Again, you can see examples both within this year and coming that will underpin confidence within that. We've talked about and we've said we're going and going to be leaders in multiple tumor types. You can see GI, lung, and breast cancer. We've said that hematology is a place that we're going to invest in. You see ECHO.
You see also here on the right-hand side, Amplify, and the work that we're going to be doing as we build it out. So as you listen to the rest of the day, we'll double click into each one of these, but we really do believe that this news flow is going to really help to lead the way to showing that we've got the path in front of us to achieve the objectives. And with that, Susan, turn it over to Sunil, who take us for the first asset. Thanks.
That was great. Thank you, David. Thank you, Susan. I think as you realize, as David and Susan walked us through, these medicines are really making a difference, and these are medicines that matter. Over the next 30 minutes or so, we'll walk you through these medicines that matter. I'll start off by talking about our targeted therapies and oral molecules, and then we'll hear from Christian and Matt talking about our ADC portfolio. Matt will walk us through the immuno-oncology portfolio as well, and then we'll hear from Anas, talking about hematology. There are some themes that I would like for you to sort of think about as we are going through it, as we're thinking about these medicines that matter. What unlocks the full potentials of these medicines by the investments that we're making today? What are the near-term catalysts?
We'll walk you through those. Then how are we bringing that strategy to life that Susan and David really talked about? Going into early-stage setting, going to make sure that we look at combinational approaches, and we'll talk about those combinations through the discussions that we'll have on the medicines that matter. So as we start off, I would like to highlight, of course, our biggest oncology medicine, which is Tagrisso, and it's really changed how treatment is delivered for EGFR mutation-positive, non-small cell lung cancer.
What started with, of course, late-line in earlier permutations in the metastatic setting, we have now brought that across all the different stages in non-small cell lung cancer, with, of course, FLAURA being the leading indication for us in the first-line metastatic non-small cell lung cancer, but also ADAURA in early stage that David talked about, and now with the ASCO plenary FLAURA, that speaks to the clinical meaningfulness of this data in stage three unresectable.
So just to orient you on the slides, the purple boxes are, of course, approved phase 3 indication, and you have the light purple, which is near-term catalyst over the next 1-2 years, that Pascal talked about, which unlocks the potential in tomorrow, and then the ongoing studies that look at combinational approaches that unlock the potential in up to 2030 and beyond, so the day after tomorrow as well. So FLAURA2 and ADAURA are the near-term, really growth drivers for us when we think about the class size that we can get in the first-line non-small cell lung cancer, and with ADAURA, of course, the duration of treatment in early-stage disease. And LAURA is going to be really important, looking at, again, the stage, across-stage coverage that we have with this stage 3 unresectable.
Then as Susan pointed out, we have these foundational assets, and now we can look at combination approaches. Really pleased to share with you, in addition to TROPION-Lung14, that you've seen before, in the first line, we also just recently posted in CT.gov, TROPION-Lung15, our combination approach with Dato-DXd in combination with Tagrisso. So this is really giving us the breadth of Tagrisso that can cover across the stage, but also how Tagrisso can be a backbone therapy across multiple lines of treatment and bringing that ADC approach. Again, as you think about the therapeutic area, leadership, and vision that we have in lung cancer, you can start to see how having this presence allows us to bring the combination power of the next generation of agents as well.
Moving to Calquence, and again, talking about leadership ambition, we remain the leaders in CLL despite the competition. We continue to see growth, and despite that competition, we are the first-line CLL leading BTK inhibitor. And you've seen the presence that we have, of course, with this asset, but in addition to that, we're growing and going into other indications. So the data that we will see for Echo at upcoming Congress shows that we will have a differentiated profile, and it speaks to the power of Calquence as not only an effective drug, but also a safe drug. And what you saw in the Echo press release, showing that there is a meaningful difference in PFS, but also a favorable trend for overall survival. Again, speaking to the safety element that really differentiates Calquence versus the other BTK inhibitors. And we have thought about the changing trends.
We've thought about where and how clinicians are thinking about the next paradigm. We have Amplify, which is going to support where clinicians are thinking about finite duration in CLL, and I think that's going to be really important. Of course, escalate coming in broader than leukemias in patients with lymphomas as well. But again, Calquence serves as a foundational backbone. As Anas walks us through the next generation of hematology assets, we have a foundation that we can build on in different indications in hematology, and that strategy is coming to life, of course, in hematology as well. Moving forward to Truqap, this has been a fantastic launch. Of course, it was approved by FDA in November of 2023 for patients with biomarkers selected HR-positive, and we've seen a strong uptake....
It has a better toxicity profile than other PI3K inhibitors, so that actually has resonated really well with the clinical community. In addition, what we have noted is that there is a great opportunity for us to have data in post-CDK4/6, where the other studies were not done in that context. So clinicians believe in this data and believe in the clinical effectiveness that is shown in this setting. We have an opportunity to build on this clinical profile, of course, now with upcoming results for CAPItello-290, which is in triple-negative breast cancer, and of course, extend what this axis can really offer and this node of inhibiting AKT, which is an important node in signal transduction, and bringing that power in prostate cancer with CAPItello-281, which is in PTEN-deficient castrate-sensitive prostate cancer.
So we have an ambition with Truqap to really address the need that we have in patients with hormone receptor-positive, expand that in CAPItello-290 in the first line, CAPItello-292 in the first line, and of course, in triple-negative breast cancer, and continue to use the power of this AKT inhibition and going into prostate cancer as well. So this is going to be an important asset for you to keep an eye on as we continue to bring important studies in this setting. Camizestrant. There was a lot of discussion, of course, of next-generation SERD two years ago. The news flow has been a bit quiet, but I think what you have probably not noted fully, but we are really proud of, is we have one of the most comprehensive clinical development program with the next-generation SERD.
That confidence comes from actually doing the right studies and having the right patients. We were the only one that did a randomized phase three, randomized phase two study, looking at the right dose of the SERD. And that gives us the belief to bring the right dose in both the metastatic and adjuvant setting, based on, of course, the important SERENA-2. And also the SERENA-3, which was a window of opportunity, gives us that proof point that we can go into the early-stage setting. We can do a study like SERENA-4. So as you take a look at this portfolio, SERENA-4 and SERENA6 are really complementary study that gives us the confidence of bringing SERD in the first-line therapy.
And then what's really unique about our SERD is we don't have DDIs with, with CDK4/6 inhibitors, so we can combine it with many of the approved CDK4/6 inhibitors. So we can also recognize the evolution and changes that we're seeing in the metastatic disease setting with different CDK4/6 inhibitors. In SERENA-6, we'll have data with palbociclib, with ribociclib, and also with abemaciclib. And we were patient. We were very patient with the adjuvant studies. There was a lot of pressure for us to say, "What is the right study design?" We were patient because we were anticipating the approvals, of course, of CDK4/6 inhibitors. And with CAMBRIA-2, we're the only phase three adjuvant study that will have a randomized component of a CDK4/6 inhibitor integrated within that design. And CAMBRIA-1 allows us to, look at that changing paradigm of adjuvant CDK4/6 in the extended duration therapy.
So I think we have one of the most comprehensive studies, and also, I think we have the confidence that we have a differentiated SERD as well. And finally, I think, Susan pointed to this. You know, having an important foundation that we have in key disease areas, having an important foundation in the scientific domain, allows us to invest thoughtfully and also increase the PTS that we have of our studies because we believe in the science. So learning from what we know from olaparib, we have been taught about how best do we think about the next-generation PARP. And Saruparib is, of course, our next-generation PARP inhibitor, which is a PARP-1 select.
What that allows us to do is to decrease the toxicities, make sure that we have greater target engagement, make sure that we have an opportunity for combining it with other assets, and make sure from a patient perspective, patients can stay on therapy for longer, derive a benefit from treatment, and also have lower dose discontinuations. That allows us to increase the likelihood of success of our studies. We have seen that emerge in the data that we just shard at ACR with the PETRA in the metastatic breast cancer setting, where not only do we have depth and durability, but when we take a look at the duration response, it's much better than what we have seen with olaparib previously and also with other PARP inhibitors.
So that gives us the confidence that we have a differentiated asset that's going to be combinable, that's going to be more tolerable, and has better target engagement. So we are going full force, of course, with this asset. In prostate cancer, we have shared with you the evoPARP-Prostate01, which is looking at castrate-sensitive prostate cancer. Again, lots of learnings we have from PROPEL that we're putting into this design of the study, looking at both HRRM and non-HRRM patient population. And of course, in breast cancer, thinking about what OLYMPIAD showed us, we recognize that patients with CDK4/6 may not respond well if they have germline BRCA mutations. So we have designed this study to go head-to-head against CDK4/6 with Saruparib. And there's a lot more to come with the Saruparib program as we think about prostate cancer, gyne cancers, and other indications as well.
So these are medicines that matter. These are really taking those learnings and bringing the foundation in the key tumor types, making sure that we have those near-term catalysts that will unlock the value, and making sure that we have the foundation to build on with the right combinations. So thinking about the combinations and the next generation, I'll invite Christian Massacesi to walk us through antibody-drug conjugates. Thank you, Christian.
Thank you. So let's continue the journey in AstraZeneca oncology portfolio. Matt and myself will go now through ADCs and next IO for us. There is no better drug to start to talk about antibody-drug conjugates than Enhertu, because it's the role model of what should be an antibody-drug conjugate. Enhertu is transforming the treatment of breast cancer. We started of course in HER2-positive disease. The drug was launched in 2019, and then 2022, we have the really transformative data with DESTINY- Breast03.
You will see soon in 2025 the data readout for the next part of the development plan, DESTINY- Breast09 frontline study guided in 2025, and also the early-stage studies, very important. We want to bring this drug earlier on to give more benefit to these patients. DESTINY-B reast 11 is the neoadjuvant study, and DESTINY- Breast 05 is the post surgery study in patient with LPCR. So this is the program in HER2-positive that will establish Enhertu as a backbone for these patients. What was very remarkable with this drug, we were able to create a new segment in breast cancer, HER2-low.
HER2-low was not existing before Enhertu, despite the patient were tested, and ultimately, with DESTINY- Breast 04, that we launched in 2022, you have seen a very meaningful benefit in PFS and in OS, and you will see the data. This is coming in a few weeks. In ASCO, with DESTINY- Breast 06, an important study because not only bring the drug one line earlier, it's gonna be fundamentally patient naive from any cytotoxic that can eventually receive potentially Enhertu, but also expand the population because the study is including also the ultra-low patient that represent 25% more patient in this HR-positive, HER2-low subgroup. So fundamentally, with the HER2-low and ultra-low, we are covering 85% of this segment. That is quite, quite, quite important going ahead. But Enhertu is not only in breast cancer.
Enhertu is changing the treatment of HER2 driven diseases across indications. DESTINY-PanTumor02 was a very important label in our view because it is for multiple reasons. The first one. The first one is, it's the first agnostic label for an anti-HER2 agent. HER2 is expressed across multiple tumor types, but it's the first time that FDA is granting a label for this. The second is the first agnostic label based on immunohistochemistry assessment. There is not a genomic alteration that is driving the patient selection, but immunohistochemistry, very easy to be used in clinical practice across tumor types. The third thing is give us confidence that this drug is working very well beyond breast cancer.
Pan-Tumor 02, of course, is a later line, represents a kind of a second, third line, fourth line option for the patient. Now, I think our job is to bring this to the patients in the same indication across tumor types earlier on. This is what we are doing through our basket studies, DESTINY-Lung03, DESTINY-Gastric03 are two good examples. We are combining Enhertu with our next generation portfolio, especially IO portfolio, because these are indications where immune checkpoint inhibitors, and in this case, bispecific, are needed. Because then our goal is to bring, of course, this combination frontline or in early setting.
Actually, this is something that we plan to do, concretely in lung cancer, in gastric cancer, in some of the GYN indications, specifically endometrial cancer, and we are planning a phase 3 that we will announce soon out in biliary tract cancer, of course, HER2-driven diseases. Let me move to the second ADC that are very much in full development, Dato-DXd, our TROP2 ADC, the second asset that we are developing together with our colleagues in Eisai. Dato-DXd, let me start with lung cancer. We had important learnings in the last months with this drug. The first one, of course, is TROPION-Lung01. TROPION-Lung01 told us that this drug is working in lung cancer.
TROPION-Lung01 is an important study because there have been many failures in second line, in second-line lung cancer, most of them recent failures across different kind of drugs, even with a competitor drug, another TROP2 ADC. And so it tells us that this drug is working, it's working preferentially as monotherapy in the non-squamous population, and this is an important learning to put together with some of the data that we are getting from the combination studies, TROPION-Lung02 and TROPION-Lung04, in which we are combining Dato-DXd with our durvalumab in Lung04 and pembrolizumab in Lung02, and with carboplatin. Susan was mentioning this. This is a drug. This is an ADC that you can combine. It's not for granted. A lot of ADCs not necessarily can be combinable, especially with other cytotoxics.
With IO, probably it's easier, but with other cytotoxic, it can be more challenging because of hematological toxicity. Dato-DXd showed that this is very possible. Carboplatin, cisplatin, are critical component of regimens in lung cancer. So this give us confidence that our ongoing plan in frontline is very well-grounded. Monotherapy activity and combinability, so TROPION-Lung07, TROPION-Lung08 are ongoing. And we are now preparing the second wave of studies, right now. We are launching TROPION-Lung10, where we are combining Dato-DXd and rilvegostomig, our PD-1 TIGIT. Matt will give a little bit more detail on the trial. And of course, as Sunil mentioned, the combination of Dato-DXd with osimertinib. This is another important aspect. We can combine Dato-DXd with osimertinib. Dato-DXd works well in EGFR mutant. TROPION-Lung01 and TROPION-Lung05 showed this is the case in terms of response rate and PFS.
What we see, that this combinability is the basis of -- and this activity is the basis of these first-line and second-line pivotal studies. Last but not least, is the biomarker. It's very important, and Susan mentioned this, to have a line of sight how we can even increase more the activity of Dato-DXd in the context of lung cancer. And this is why we are integrating concretely in phase 3 programs now the QCS TROP2 biomarker. TROPION-Lung10 and Kulasa Avanzar are the two examples that we are pursuing now. Breast cancer. Breast cancer, another important indication for Dato-DXd. You have seen TROPION-Breast01. TROPION-Breast01 is a positive study, not only because it showed that Dato-DXd is better than any other standard of care, but also for the safety profile they showed.
We have half of the adverse events that the comparator arm, far less than was shown with other similar drug in the same setting. This gives us confidence on what is fundamentally our key activity in breast cancer, this triple negative. In triple negative, we are using dato-DXd as monotherapy or in combination with Lenvima, based on BEGONIA data, in TROPION Breast 03 or 4 and 5, early setting and frontline. Of course, dato-DXd TROP2 expression is not only limited to lung and breast. This is where we are investigating the drug as a monotherapy and combinations in Pan-Tumor 3 and Pan-Tumor 1, the Sanctua platform studies, in which we are exploring multiple indications and where we also wanna, of course, integrate the biomarker. Matt, what about our ADC?
That's right. So as you've heard, hopefully repeatedly throughout, this morning and into this afternoon, a core focus for us on oncology is replacing historical chemotherapy with ADCs and radioconjugates. And just building on the success and growth opportunities that you just heard from Christian related to Enhertu and Dato, our confidence is only strengthening as a result of that data. But of course, we're eager to build even further. As you heard from Susan in the beginning, this is just the beginning. And so on behalf of creating that portfolio that allows us to be able to cover spaces beyond breast and lung cancer and to bring this vision to life across the wide space of cancer, we've been investing longitudinally and at scale to build the comprehensive toolkit that's needed in order to bring these ADCs to life.
And Pooja Sapra, who leads our oncology targeted discovery platform, has had a few key pillars for how we're investing in the diversity that's needed in order to bring the best of these assets to patients. That includes a diversity of payloads, as well as the linker technology, the antibody formats that allow us to target new targets, as well as the comprehensive proteomics that allow us to identify first in human targets, to be able to put the totality of this together in an industry-leading end-to-end platform that allow us to give us the confidence to be able to create the breadth of a portfolio that achieves and matches our ambition. Next slide. To complement the portfolio build, you've heard a little bit already throughout this session about our commitment to biomarkers and our success in bringing precision therapies to life for patients.
So I wanted to take a little bit of time to talk a little bit about how we're thinking about the next generation of biomarkers for ADCs. QCS has been alluded to, and so we'll take a little bit of time just to talk about what it is and what we know so far. If we look at the sort of the brown stain on the far right, that's the classical IHC that underlies so many biomarkers today. You can imagine if you were a pathologist looking at that image, you might be struck with a few challenges. How do you differentiate what expression is where? How much of it? How different is it from one cell to the next?
And so what QCS allows us to do is a human-trained AI-enabled pathology tool to be able to take the brown picture and transform it into the green and blue picture you see just to the right of it. What it does is it allow us to be able to identify and distinguish tumor versus normal cells, and to be able to specifically quantify the amount of expression and where it is. So you can see the difference between what's on the surface of the cell, what could be on the inside of the cell, and how do we imagine those differences in addition to the changes between the tumor and normal?
This is what gives us so much excitement about the power of computational pathology and why we think this is a revolution that's at our fingertips, and why we're so proud to be leading that revolution with QCS. So if we turn to the right-hand part here and use TROP2 as just one example, we're proud of the way that TROP2 has been a key success in second-line lung cancer and other diseases. We can imagine that as we move to earlier lines of therapy, the opportunity to be able to pair this with a biomarker might be particularly critical. But the challenge of TROP2 as a biomarker, at least in all previous efforts, is that IHC doesn't work. Just to look back to that brown stain, expression is sort of everywhere, at least to the naked eye.
We've needed a new biomarker to be able to identify how can we bring TROP2, ADCs to the right patients. What we've found so far, using some of our biological preclinical data, is that in contrast to IHC, QCS associates with the internalization of the ADC, which is what's necessary for it to work, as well as the site of toxicity, the amount of cell death you get in a preclinical experiment. Fundamentally, QCS underlies the biology of how an ADC works and gives new insight to the mechanism of action. But most importantly, in some retrospective analysis, in J101 and some other studies internally, we've seen for the first time that QCS is allowing us to be able to predict efficacy.
We've applied these retrospectively thus far, and we'll talk a little bit later on our opportunities to prospectively apply this. But this is what gives us so much excitement about both the breadth of our ADC portfolio, the ability to bring new biomarkers, and a whole new field of computational pathology to be able to achieve the scale of replacing chemotherapy across key diseases. It also highlights our commitment to patient selection. Pascal mentioned in the very beginning how a core equation for our success in oncology represents combinations of ADCs, IO, and patient selection. This is how we're able to accomplish that, and this is how we differentiate ourselves from peers.
So as you've heard a bit about our commitment toward our internal portfolio, as well as our commitment to new technologies that drive patient selection and combinations, this is what we imagine the future to look like. This is our vision for ADCs in oncology. If you go back to the slide that Susan began with, highlighting the unmet need across cancers, this is how we imagine filling that unmet need, with specific targets and a repertoire and a differentiated diversity of warheads to be able to match the right differentiation of targets across key diseases. We've talked a little bit about our progress in lung cancer and breast cancer, but of course, our ambition doesn't stop there. This opportunity is a key example of how our ambition can be big and broad, but also focused around a core idea of how to replace chemotherapy as ADCs.
It's also not just an idea. We have the concrete assets, targets, and warheads that are either in or near the clinic today to be able to accomplish this, and you can see some of the targets that are highlighted at top, across the top. Fundamentally then, we have the portfolio diversity, we have the track record, we have the expertise, and we have the investment to achieve this scale of investment, this, this scale of ambition. But just to go just one level deeper, briefly, on behalf of our internal portfolio to come, we now have six proprietary ADCs that are in the clinic today, and these six represent a diversity of, of new as well as, targets where we're trying to pair the right warhead on validated targets. So, for example, our claudin 18.2 ADC is a validated target for the monoclonal antibody.
We know that that can work in gastric cancer, and it's one of the largest segments, if not the largest segment, of gastric cancer. But building on our success within HER2, if you take a target and pair it with a great ADC, you can achieve transformative benefits. And that's what we see on the right here with the waterfall plot from our—these are more heavily treated gastric cancer patients, all selected for claudin 18.2, and you can see that nearly all patients have a downtrending response. We saw about a 40% response with this monotherapy in patients with claudin-selected gastric cancer. This is a sort of response rate that gives us the confidence that ADCs can and should replace traditional chemotherapy across cancers. But like I said before, we're not stopping there.
Gastric cancer may be part of our next frontier, but we have targets like B7-H4, which has the potential to be a first-in-class target for places like endometrial cancer and beyond. EGFR/c-MET is, again, an example of a validated antibody target, where we hope that by adding an ADC to it, we're able to both deepen the responses that are possible, as well as extend the diseases that can be responsive, extending to places like EGFR wild-type cancer, as well as potentially colorectal cancer. As well as folate, which, again, is a validated target and one in which ADCs have worked in ovarian cancer.
But we think that the success of things like in HER2, in ovarian cancer have highlighted, what if you could bring an even better warhead to a great target so that our ADC construct is the topo warhead plus the folate target to be able to conquer places like ovarian cancer? That this sort of theme continues through our hematologic portfolio and is an example of the breadth of the opportunity that we have. On behalf of the news flow that you can expect from us over the course of this year, we have an encore presentation of the claudin 18 ADC at AD ASCO in just two weeks, and I'll have slightly updated data.
And then we're also really excited for the first time to be able to bring new data on behalf of our B7-H4 ADC, as well as our folate ADC, to congresses later this year. So with that, well, I hope to have given you a sense of how we can bring our ADCs to replace chemotherapy, pair it with patient selection to achieve this core equation for how we're bringing success to oncology. But another key part of that is IO, and so I'm gonna pass it back to Christian to talk a little about that.
We cannot win without going to the next level in the immuno-oncology space. Let me start actually where we are, in Imfinzi Imjudo. Imfinzi Imjudo is doing very well in the marketplace, but I want to say that you see this as an enabler for our next steps. First of all, we already mentioned how Imfinzi and Dato-DXd combinations represent the first IO ADCs that we brought into phase III in lung cancer with abadzar and in triple-negative breast cancer across three phase III studies. Imfinzi is also helping us, you will see the ASCO plenary for Adriatic, is helping us to consolidate our leadership in some indication that will be in scope going ahead with our portfolio.
Small cell lung cancer is one of them. ADRIATIC is a very important readout and because it's incredibly meaningful for patients for decades in which there has not been any advancement in limited stage, and also because it consolidates our presence, of course, with CASPIAN and what we are building in this indication. Imfinzi and Imjudo allowed us to enter GI. That is our next big indication for AstraZeneca Oncology, after lung and breast. We are building on Himalaya, the success of Himalaya. You have seen the readout of EMERALD-1 . And of course, there are other studies that are ongoing in this space. We are investing heavily with EMERALD-2 and EMERALD-3 , and we will bring our next combinations in this space of HCC.
MATTERHORN is an important study because it gives us a competitive advantage versus the other companies, because it can be the only checkpoint inhibitor with durvalumab in the perioperative space for gastric cancer, after, of course, some other studies failed in the space. We met the first endpoint, pCR. We are waiting next year for the EFS, that is the key hard regulatory endpoint that ultimately will allow us to file it. And of course, TOPAZ, we are maxing out commercially the BTC space with TOPAZ with Imfinzi. It is an important aspect because we want to do more in this space.
Actually, we already started the first Phase III study with Rilvegostomig in the adjuvant space, based on the learning that we had with Imfinzi. So this is also an indication where actually we launched the first PD-1 TIGIT Phase III studies, and I already mentioned before in ERTO. But our next drugs, next portfolio will allow us really to displace the current PD-1, PD-L1 inhibitors.
Indeed, we're very excited about the opportunity to displace PD-1 monotherapy, and we have a vision of how the IO-sensitive space has the opportunity to be sub-segmented by complementary medicines. So Mark Cobbold's team have developed a few IO bispecifics that bring the power of PD-1 together with additional targets that harness distinct T-cell biology, that bring the power of IO together in one molecule. And so Christian set this up to start about Rilvegostomig. Rilvegostomig is our PD-1 TIGIT bispecific, and we know from external data that TIGIT really can bring additional benefit, particularly in the IO-sensitive spaces, like in PD-L1 high lung cancer. And we have preclinical data that says that the bispecific format has the opportunity to unlock distinct biology.
By being able to coordinatedly interact PD-1 and TIGIT together on the same cell at the same time, we're able to strengthen the immunologic synapse and to drive distinct immunologic benefit that was seen preclinically. But it's particularly the safety profile of TIGIT that we've seen both with our own molecules, reported in the post-IO space, as well as others, that make us dream about what's possible when we take the power of PD-1 plus TIGIT through other combinations that access the adjuvant space. Christian's alluded to our opportunity in adjuvant biliary cancer is just one space already, as well as in combinations with chemotherapy. But it's the power of our ADC plus IO combinations that we think have the real opportunity to unlock differentiated opportunities.
We have a comprehensive development program applying Rilvegostomig across multiple of our ADCs here, and we're excited to be able to bring an update of our Rilvegostomig experience a little later this year. We've shown you data from the post-IO experience, which again, has highlighted the convenience as well as the very clean safety profile of the bispecific molecule. And a little later this year, we'll bring you the first data of our experience with Rilvegostomig in the IO-naive, PD-1 positive patient segment of lung cancer, a place where we know that TIGIT can particularly work and contribute. So Christian had alluded already to this key study, the TROPION-Lung10, and we wanted to highlight this for a particular, for a few particular reasons. Because it's an exemplar of what we're trying to do across development of our portfolio.
It represents, first and foremost, so the opportunity to replace, displace single-agent IO with new segments of our new wave IO. We're bringing TIGIT, in addition to PD-1, to replace what is currently a standard of care. It's also an example where we're trying to combine this with our ADCs, so by bringing an arm in which we have dato and Rilvegostomig together. But thirdly, is the opportunity to do this in the context of key patient segmentation. This is a place in which we're already using Rilvegostomig in a space in which we expect it to have its most benefit, in the PD-L1 high space of lung cancer, but adding the QCS TROP2 selected opportunity to maximize the benefit of TROP2 when thinking about how do we bring this to the earliest lines of therapy.
This is just an example, and it's a key study for us, but it's an example of our development paradigm coming to life. But it's just one example of the scope of our opportunity with Rilvegostomig, and it's one of 10 studies that we have the opportunity to be able to start for pivotal programs, thinking about just lung cancer, but also beyond, in terms of GI cancers, gynecologic malignancies, and beyond. And then the other key IO bispecific that Susan mentioned before is volrustomig. We think a little bit about the IO-sensitive space, breaking into places in which TIGIT can most benefit in those IO-sensitive spaces, and other places in which our own data, as well as other experience with CTLA-4, have highlighted distinct sensitivity to CTLA-4. And this IO bispecific is specifically designed to do things that prior CTLA-4s haven't been able to do.
The bispecific format, in particular, the monomeric bispecific format that we have, that other, different than other bispecifics, allows you to be able to saturate PD-1 wherever it's expressed, so it's an excellent PD-1. But it particularly engages CTLA-4 in the context of PD-1 positive T cells. So it's getting the amplified effect of CTLA-4, particularly in the T cells that can most be active against the cancer. These are the anti-cancer T cells that we think can drive most benefit and start to dissociate the potency of CTLA-4 from the toxicity that has historically prevented it from being able to achieve those potencies. And in terms of our clinical experience, we've shown how, as we transition this molecule, the biology is delivered. We've achieved a degree of T cell proliferation that hasn't been previously possible when PD-1 and CTLA-4 were given separately.
We always struggled with toxicity well before we could achieve that potency, and so we're really excited to be able to see the differentiated pharmacodynamics at action and the thesis of this molecule ultimately playing out. But it's not just pharmacodynamics. We've also seen differentiated efficacy in key places where CTLA-4 is known to work. That includes kidney cancer, as well as PD-L1 low lung cancer, which is this waterfall plot that's shown in the middle. Again, nearly all patients with descending tumor responses and differentiated efficacy with response rates in the PD-L1 low segment that hasn't been previously seen with chemo and PD-1 itself alone. And so because of that, we've initiated several phase III studies.
The EVOLVE Lung 02 is a key one, which represents sort of the extension of the phase I/II experience that we have here, targeting again, the PD-L1 low segment of lung cancer. This is a fantastic example in which we have a key clinical unmet need, matching known biology and bringing a differentiated molecule in the context of a combination to patients who most need it. But of course, we'll continue to extend beyond PD-L1 low lung cancer in other places where CTLA-4 is known to work, including mesothelioma, cervical cancer, and head and neck cancer.
Again, in terms of updated news flow you can expect this year, we've reported previous data in kidney cancer, as well as our initial experience in frontline lung cancer, and we look forward a little later this year to be able to bring some updated data from our experience in frontline lung cancer in combinations with chemotherapy. So before we end, I'll pass it back to Christian to show how it all comes together.
Yeah. You have seen the ambition, you have seen the framework, and you have seen the modalities, small molecule, ADCs, IO. Now I wanna give you just an example how we approach the development plans of these drugs. Let me start with two indication where we are already leading, and we wanna continue to lead even more: lung cancer and breast cancer. These are tumor maps, are simplified tumor maps. In your material, you have the complex one with all the trials, all the colors, but we tried to make this simpler, just for the sake of the this presentation. In lung cancer, the tumor maps are taking consideration the setting of the disease and the key subgroups that of course require often different treatment and different approaches.
In lung cancer, you have a space that is IO sensitive on the left side of the slides. In IO sensitive, fundamentally, what we wanna continue to do is continue to establish Imfinzi as the key Stage III drugs, and in an early space, we have all the Pacific series studies. In metastatic setting, dato-DXd should become the backbone ADC for every combo, IO combo, and hopefully, we will be able to move also earlier on in the early space. But the real big challenge that we are taking here is to replace PD-1 and PD-L1 inhibitors with our bispecifics, Rilvegostomig and Volrustomig. This is in IO sensitive space. In EGFR space, of course, Tagrisso is the clear drug. We wanna continue to build on Tagrisso.
ADCs are playing and will play a role in this space inevitably. Dato-DXd showed very strong activity as a monotherapy and is combinable with Tagrisso, and this is the purpose of TL15 and TL14. We will have additional ADC that can play a role in this space. Matt mentioned EGFR/c-MET, and so more potentially can come. Breast cancer. Breast cancer, HER2, HER2 positive space is the playground of Enhertu. I don't even mention that. We talk about that. HR-positive is more segmented. When the disease is still very much endocrine sensitive, we see camizestrant as the key endocrine therapy to be used in any combination, in early setting and in advanced setting.
When disease start to develop some resistance to endocrine therapy, becoming less endocrine sensitive, we can address some of this resistance with our AKT inhibitor, Capivasertib, Truqap, and of course, make a lot of sense to combine Truqap and Camizestrant going forward. When the disease and the patient needs unfortunately cytotoxics, this is the moment in which we plug in our ADCs. Enhertu for HER2-low and HER2 ultra-low, and Dato-DXd for HER2-null patients. Triple-negative breast cancer, Dato-DXd is the key backbone as a monotherapy, and even more in combination with Imfinzi. Gastric cancer. This is where we—HCC, we are already playing an important role, and we wanna do even more. BTC, I think we are already covered that space. Gastric cancer is the next big indication where we wanna play.
We already have today a good starting point. First of all, it's an important market, and we already have Enhertu approved in Enhertu space. We are waiting MATTERHORN with Durvalumab in the perioperative space, and we launched the Phase III study with our AZD0901 Claudin 18.2 ADC in second or third line. But what we are doing is developing the next generation combinations, our bispecifics with our ADCs. DESTINY-GASTRIC03 and GEMINI are platform studies where we are combining Enhertu and rilvegostomig, volrustomig, and our Claudin 18.2 with the bispecifics. We wanna bring- of course, this combination in frontline in the perioperative space. So I hope I give you a flavor how we're approaching the development of this very rich portfolio in the context of the key indication where we wanna win.
And with that, thank you for listening to us, and I pass to Anas to deep dive into hematology.
All right, thanks, Christian. You just heard about our bold ambition in oncology. The next 10 minutes, I will introduce you to our hematology pipeline strategy and our ambition to be a leader in hematology also. You've heard from Susan and Pascal and many other colleagues about the power of combinations, and our core element of our strategy is to build combinations very quickly in hematology to improve the treatment outcome and a potential cure. And for that, we're developing more than one drug for the same indication at the same time, using different mechanism of actions. So we have ADCs, cell therapy, T-cell engagers, and small molecules. And these are not me-too drugs. These are. There's a good level of innovation and differentiation. I'll walk you through some of these examples.
So the CD123 ADC, this is the first ADC in hematologic malignancies with topo I warhead. First one. GPRC5D ADC, first ADC targeting GPRC5D for multiple myeloma. The cell therapy program, it's the first CAR T-cell therapy with two antigen targeting for multiple myeloma, targeting BCMA and CD19. T-cell engagers, first CD19 T-cell engager, full length, that allows intermittent dosing, and with improved safety profile because it has low-affinity binding for CD3. And we have a T-cell engager for CD20, which is the first T-cell engager for any indication, not just for hematologic malignancies, that preferentially binds CD8, therefore sparing activation of CD4, which is associated with a toxicity, especially cytokine release syndrome. Oops! All right, so how do these drugs stack against different indications?
So for B-cell malignancies, now we have two drugs that are combinable, Calquence and the CD19, CD3 T-cell engager. I'm not showing the CD20 T-cell engager here because it's not in the clinic yet. It will be in the clinic in next couple of months or so from now, and then they will show up there. And actually, the first combination has been cleared by the FDA to go with the CD19 T-cell engager plus Calquence for the two major indications where Calquence is approved, CLL and mantle cell lymphoma. Initially, it will be in relapse setting, and we have planned to rapidly move this combination to the frontline setting. For multiple myeloma, we have two assets, the CAR T-cell and GPRC5D ADC, and there's more to come with different mechanism of actions.
For AML, we have a CD123 ADC, as I mentioned, with the novel, topo I, warhead. There's more in the pipeline to come to allow us for these different, combinations. So next few minutes, I'll walk you through our, 2 leading assets, with a little bit more details. The first one is our, T-cell engager targeting, CD19 and CD3. As I mentioned, this is a full length, so it allows us to dose every 2-4 weeks. Initially, we started with intravenous. Subsequently, we'll be doing subcutaneously. It has a low-affinity binding site for CD3, so it has a lower, side effects, compared to other, T-cell engagers.
Actually, if you look at the pure biology from target selection, CD19 is much better than CD20 because it has a broader expression profile and is expressed earlier in the B-cell ontogeny compared to CD20. So you have the ability to kill the precursor B lymphocytes in multiple B-cell malignancies, and therefore, you have deeper responses and eradication of minimal residual disease. But in reality, I think you need both for combinations. That's why we're building two T-cell engagers, one for CD20 and one for CD19, to address tumor heterogeneity and antigen loss. But just to show you how powerful this T-cell engager, you can look at the table on the right of this slide, focusing now on only follicular lymphomas as an example. 88% overall response rate, 82% complete response rate.
You don't see this response rate and CR rate with any single agent for B-cell malignancies. The only time you see this high response rate and CR rate is with CAR T-cell therapy. So this is as good as CAR T-cell therapy they've been approved for this indication. We have a broad development plan across all B-cell malignancies that are ongoing, and you'll have updates about these responses in upcoming meetings. The second asset, which we're also very excited about, is this biCAR, which target two antigens for multiple myeloma, CD19 and BCMA. Again, this is very differentiated. We know that there is two CAR therapy products approved for multiple myeloma targeting BCMA. This is different in multiple aspects. One, as I said, it targets CD19.
There is small proportion of multiple myeloma cells that express CD19, less than 0.001% probably, that have the capacity of being self-renewal. So these are the precursor cells for multiple myeloma, and therefore, if you target CD19 on top of BCMA, there's a chance that you have a deeper responses and higher chances of eradicating minimal residual disease. It also uses a rapid, fast manufacturing platform, which means that not only you can produce more CAR T-cells and treat more patients, but also allow us to use a smaller number of cells for each patient with more fit young T cells, and therefore you can have a powerful treatment with reduced side effects.
Again, I'll show you the example here on the left side with the bar graphs of the response rate and CR rate that emerge from frontline newly diagnosed patients with multiple myeloma that are transplant eligible. So frontline treatment landscape for multiple myeloma is divided into transplant eligible and transplant ineligible. Transplant ineligible is about 70% of patients, eligible about 30% of patients. These are traditionally treated with induction combination therapy, like 4 cycles, followed by autologous transplant, followed by maintenance. And if you take the high-risk patients in this group, the expected outcome of this four-drug regimens, transplant, and maintenance, CR rate is about 50%-60%, and MRD negativity about 50%-60%.
And we're seeing now it's about 100% overall response rate, CR rate more than 90%, and eradication of a minimal residual disease by about 100%. Very remarkable early results, and that's why we're all so excited about it. With this, I'll stop here, and I'll hand it back to Susan, and thank you.
Thank you, Anas, and I hope that gives you a sense of why we think the hematology portfolio is somewhat underappreciated. So let's go on now and talk about a little bit about the day after tomorrow, the transforming outcomes with the next generation therapies. So I wanna spend a little bit of time talking about our radioconjugate ambition. I actually trained as a radiation oncologist, and I've long wanted to change the paradigm of how we actually treat patients with radiation therapy. It's a very effective therapy. Nearly 50% of all cancer patients get treated with radiotherapy at some point in their treatment. But what we have to do with external beam radiotherapy is treat from the outside in, and that means going through normal tissue.
The key limiting factor why we can't cure more patients with external beam radiotherapy is the normal tissue toxicity. Spend a lot of time optimizing the anatomy to avoid critical structures like the spinal cord, that can only tolerate 45 gray of external beam radiotherapy. That means quite often you're relatively underdosing compared with what you need for cure of the tumor. Radioconjugates can treat with radiation therapy from the inside out, and what that can mean is a reduction in the dose to the normal tissues. This could supplement and reduce the total dose of external beam radiotherapy that you need, or in some cases, in time, it could be something that could replace the current standards of care. One thing that is important in terms of this is it unlocks target space that is different from antibody drug conjugates.
You don't need to internalise to deliver the radiation therapy to the cancer cell. You can use small molecules with different half-lives that can optimize the therapeutic benefit. We can put these pieces of the puzzle together with some of the capabilities that you've already heard Matt talk about, that Pooja Sapra and her team are, are building. And importantly, radiation therapy, with some examples that we've already got, PACIFIC trial, for example, shows that it combines well with immunotherapy, so it's a critical component of how. And that's because the mode of death that you get with radiation is a very immunogenic form of cell death. And particularly, if you can avoid dosing the lymph nodes, you will increase the therapeutic window and potentially increase that combination.
So that's why we're excited about the potential for radioconjugates, and why we're excited about the acquisition that was announced, of Fusion, which of course has not yet closed. But let's give a little bit of data about the lead asset that Fusion has, the PSMA alpha emitting radioconjugate. So first of all, with the data that has been established with the Lutetium PSMA, a beta particle emitting radioconjugate from the VISION trial, you can show the potential of this to improve outcomes, this case in prostate cancer, because PSMA is highly expressed in prostate cancer. But what we've got with the collaboration initially with Fusion and then the potential acquisition, is access to alpha particle emitting radiotherapy, right?
So for those of you that haven't done physics, let me just try and explain a little bit. An alpha particle is much heavier than a beta particle. Beta particle has the mass of an electron, alpha particle has 2 neutrons and 2 protons, much, much heavier. So it doesn't travel as quickly, and it gives up its energy very rapidly as you go through the tissue. I'm getting smiles in the back. Good, means you're focused. Excellent. But you can see on that middle panel that you've got the linear energy transport, or the energy deposited per unit length is much greater for an alpha particle than a beta particle. What that means is it's delivered very close to the cancer cell that it's targeted to. That means there's lower dose to the surrounding normal tissue.
There's actually been a retrospective meta-analysis published in Lancet Oncology that's shown in the bottom part of that middle panel, which shows that you actually can translate through into an improved response rate for the same target with an alpha particle emitter for the PSA 50 here. Again, the point about the potential for combination with IO is shown on the right-hand side of this slide, looking at a combination of an anti-PD-1 antibody with an actinium emitting tumor targeting alpha emitter in this context. This is a CD26 example. And again, we have, through our collaboration, built more of these examples. We look forward to bringing these combinations forward into the clinic....
So that's a little bit about some aspects of what's for tomorrow in terms of the radioconjugates. Now let's move on to cell therapy. You've heard already from Anas about some of the excitement of the Gracell, AZD0120, asset, the BCMA CD19 for multiple myeloma, and you've also heard from Sharon and the team about the excitement about what that can bring into immunology diseases such as SLE, which again, have that outcome that's not dissimilar from patients with cancer. What I'm also very excited about is the solid tumor portfolio of cell therapy that we have built over the last three and a half years, led by Mark Cobbold's team, and that's been expanded through our acquisition of Neogene, with access into the T cell receptor therapies.
Our lead asset is a GPC3 targeted cell therapy. GPC3 is a target that's highly expressed on hepatocellular cancer. But what is different about our GPC3 cell therapy is that we've got an armoring in there. Armoring enables the cell to overcome the immunosuppressive microenvironment. In this case, we've got a dominant negative TGF-beta armoring. Now, there are many GPC3 cells that have been taken into the clinic, many in China, but this is the first with this armoring. And we've got some exciting data that will be presented at ASCO. We showed a teaser for that at AACR last year with a small number of patients. Very encouraged by the data, and I look forward. Please go and see that. Don't just be distracted by the plenary sessions with the two and the thing, and the REST06.
Go and have a look at this presentation as well. Behind that, we've now got a STEAP2 with the same armoring, the dominant negative TGF-beta. This is targeted at prostate cancer. So you may have heard of STEAP1. STEAP2 is even more specifically expressed in prostate cancer. It's a, it's a target that we have a great deal of excitement about, and we're not just developing cell therapy there, we've also got other assets that are using this, this target. We know that both liver cancer and prostate cancer are tumors where there's high levels of TGF-beta, and that's why that, that armoring mechanism is particularly important. And we've also got a claudin 18.2 dominant negative TGF-beta for gastric cancer. With Neogene, what we're hoping to do is develop therapies to a broader range of targets.
So many cell surface targets have been exploited already, but what the Neogene technology does is enable you to target targets that are intracellular and that are expressed in the context of MHC, and for that, you need T cell receptor therapies. These are about targeting shared neoantigens that are uniquely expressed on the tumor. We have the TP53 R17H targeted mutation, and also a KRAS G12D. So our goal for cell therapy is to deliver all these effectively, but what's really key to winning this space is you've got to be able to deliver high-quality cells predictably to spec.
This is one of the advantages that through the Gracell acquisition and then FasTCAR process, it gives us access to, together with the excellent team that we've that we got through the Neogene acquisition, that had experience in delivering CAR-T original cell therapy. So we've got plans to make sure that we can deliver high-quality cells in spec with the capacity we need to meet this clinical scale of what these kinds of opportunities would bring, and deliver that profitably, through decreased cost of goods. So with that, I hope that is exciting you about the day after tomorrow, and I'm gonna hand over to David to sort of bring us home. Thank you.
Thanks, Susan. I appreciate it. So thank you for coming along with us on the journey of reimagining what cancer treatment might look like in 2030. And we started with Susan walking through and talking about some of the mega trends that are creating that future, and I'd argue that we're at the vanguard of many of those trends. And I also hope that we brought today reasons to believe together for you to be able to see that this is not just science fiction, but actually something that is factual and coming to reality. Susan, if you go to the next slide. And this, of course, is critical for the ambition, the mission, the meaning, the purpose that we all have to be able to really make progress against this goal of eliminating cancer as a cause of death, and it generates value for shareholders.
I think that that is something that, again, I hope that we're able to really demonstrate and bring out and share today. You see here in the upper left-hand corner, for all of you on your left, the number of assets that we see as having a $5 billion+ potential. Many of those are known. Obviously, you're all very familiar and ask us infinite questions on Tagrisso, Imfinzi, and Enhertu. But I would also say that it's important to note that we articulated, and I think that you heard throughout all the presentations, the depth that we went into, eight other new NMEs or seven NMEs, plus the collection of AZ ADCs that are important to know.
People say, "What are the three things that I need to know in oncology?" And I'm afraid the first one you need to know is you got to model out eight new NMEs. I can't help you on that. But I think once you work that out, you have an opportunity to have an appreciation for why we see that we're on a trajectory and have the opportunity to be the number one oncology company, and we say that with humility, and we say that with recognition of those that do sit in front of us, at least on a revenue basis. We'll be reading out key phase twos and phase threes over the course of the period in front of us. I think that, again, if you take a look at what you see on this, you see two bispecifics, you see multiple ADCs, you see targeted therapies.
You see that we're moving into early, you see demonstrations that we're moving into combo, and you see hematology really emerging in a very important and real way. These are all things that we've spoken to. So come join us at ASCO. We'll get a chance to see you there. We'll serve some good coffee on the Congress floor, so when you get bright and early up for DB06, then you'll be well-powered as you go into two plenaries. We'll have some AZ6 pins out there, and it'll be fun. With that said, it is my distinct pleasure to invite Aradhana up to bring us into the financial close. Thank you.
Thank you, Susan. Thank you, David. Thanks to all of you for being here today and for hanging through the post-lunch afternoon and not sleeping. But I do not have a fancy video, unlike all of my colleagues. No video to start off the finance section, but we always save the best for the last. So, how are we bringing all this together, all the excitement that you heard, all the energy that all the colleagues here brought into delivering shareholder value? This is AstraZeneca's shareholder return over the last 10 years, and you can see we have performed obviously really well, thanks to the support of all of you shareholders. But also compared to all our peers, the pharma index, we have performed really well. And we don't sit on our laurels.
We're continuing to invest, as you've seen today, to continue this momentum into the future, and not only over a long-term period, but even if you look at the last 10 quarters, we've actually met or exceeded consensus estimate on both revenue and EPS. You've seen over the last several quarters that our top-line momentum continues to be very, very strong. If there's one chart that you take away from today, it's this one, and Pascal covered this early today. But also, each of the sections you saw had a similar chart, which looks at what's our current base in 2023, what the next step will be in the portfolio. In that second bucket, there are two key elements. One is the existing products with existing indications, and that also includes geographic expansion. Many of our medicines are still launching across the globe.
Many of our medicines, for example, in respiratory, are still very early into that journey, have 10+ more years to go. So again, in that existing portfolio, there are two buckets. There's the existing medicines with the existing indications, and there's existing medicines with LCM opportunities, many of which you heard today. And those LCM opportunities, one would argue, are relatively lower risk as we expand into greater indications. The third bucket is the new molecular entities. This is where we have a very ambitious target of 20 new molecular entities by 2030, and we'll double-click a little bit into that. And then it's the day beyond, the day after tomorrow, and you heard a lot of new technologies that we're investing in that, again, we think will transform care beyond 2030 and continue that momentum.
I know today was a very, very overwhelming day, and there's a lot of information shared, but we do believe the breadth of our portfolio is our key strength. That does not mean we're dependent on one particular asset. We have a very broad portfolio, and again, not everything will work. That $80 billion is a risk-adjusted number. More importantly, that $80 billion ambition is not based on any M&A. That is based on the assets that we have in hand today, and we hope to deliver on them. So double-clicking into that second green arrow. Again, there are several buckets into that second green arrow. There's the billion-dollar opportunities, the $1-$3 billion, the $3-$5 billion, and the $5 billion plus.
Obviously, it's a lot to fit on a page, but these are the five plus within those new molecular entities in that second arrow, and we expect most of these to launch by 2030. Now, the peak sales will be obviously much beyond 2030, but again, we expect that as de-risking happens... Pascal talked about you will have data events in 2024. You'll have data events in 2025. As that portfolio de-risks, you'll have more and more confidence in these new molecular entities and the potential for these to be, whether in the $3 billion bucket or the $5 billion bucket, to contribute to our ambition. Today, we have 13 blockbuster medicines. We expect that by 2030, we will have 25 potential blockbuster medicines, and we could even have more.
As you can see, the list actually is more than 25, but again, that's at least the minimum we hope we will have on a risk-adjusted basis. I think there was a question asked earlier, and we get this question a lot from investors as to why do we believe we have higher productivity, and I think as you've seen data and our productivity in our pipeline, why is that the case? So I wanted to share a little bit about what is our operational model that drives this organizational productivity.... When we look at resource allocation, we look at resource allocation on a total portfolio basis. So it's not only oncology or rare disease or biopharma. Every drug and every project has to stand on its own merits, and the portfolio prioritization is based on a variety of metrics.
It's based on what the commercial potential is. It's based on what the risk is. It's based on what the execution could be. It's based on competition, and it takes into account all of those metrics and how we can create value, and what are the best molecules that we should invest in to create value. We also look at how we're developing these molecules and how the actual execution's gonna work. That means we have very rigorous technical reviews internally. We obviously seek advice from a lot of experts, and you've seen today the work that we're doing on biomarkers as well as patient segmentation. We're also driving operational execution. Over the last several years, we've actually internalized a lot of our clinical studies, and we've done that not only for the economic benefit that it has, but also to be able to better control data.
We're trying to shorten the time it takes from concluding a study to actually getting the registration done, and not just in major markets, but across the globe. That, again, drives value from these medicines. Lastly, our process and incentives are aligned. We have an annual prioritization process. We're constantly optimizing, and again, this takes into account not just our internal molecules, but also many of the BD opportunities that you've seen and heard from us today and, you've seen over the last several months. Ultimately, I would say it's our people. You got the opportunity to hear today from some of the brightest minds in each of these areas, but it's really our people and the collaboration because this is a complex, complex space. It takes a lot of collaboration to actually bring any of these medicines to market. Our focus on cash conversion continues.
You've seen our cash conversion and cash generation improve over the last several years. Again, as we returned to revenue growth in 2019, 2020, we started our focus on cash conversion, and you can see how that's improved as a percentage of revenue over the last several years. Our capital allocation priorities have not changed. Our first capital allocation priority: reinvest in our business, and I'll talk a little bit more in detail about CapEx in the next slide. Second capital allocation priority: maintain a strong investment-grade rating. When we did the Alexion acquisition, we had taken on leverage. Over the last several years, we've reduced that leverage, and we're in very strong position from an investment-grade standpoint. Our current net debt to EBITDA stands at around 1.9 times. Our third capital allocation priority: business development.
Over the last 18 months, we have done 10+ transactions, and we've spent about $6.6 billion. I believe we have been very, very disciplined, very, very strategic, and very, very prudent in terms of how we have allocated that capital. We have not spent $10 billion on one asset, and you've seen today some of the excitement, how we're transforming and driving cell therapy, radiopharmaceuticals, new modalities in vaccines. So all, all of this business development, I think, has been very strategic and very disciplined. Lastly, we maintain a progressive dividend policy. We raised our dividend in 2022, and then most recently, at our annual meeting, we raised our dividend again.
Progressive dividend policy means that we will look, and the board ultimately makes the decision, but we will look at all our capital allocation, and we will be raising dividends when we believe we can. I know some of our colleagues are focused on dividends, but we do maintain a progressive dividend policy. I wanted to go into a little bit of detail into capital expenditure and how our CapEx is supporting our future growth. For this year, we gave guidance that our CapEx is gonna be 50% higher than it was the prior year, and there are four particular projects that are driving that higher level of investment.
The first is an inhaled facility that we're building in Qingdao, and this is really to help support the inhaled products, Breztri, for example, and the demand that we expect from asthma and COPD in those emerging markets. So this is China for China as well as the greater emerging markets. We're building a new API facility in Ireland, and this, again, is to make sure our supply chains are robust. These are particularly for high-value APIs. We announced a cell therapy facility in Maryland. You've seen Susan's cell therapy ambition, and this is to support that, and we believe we will again look for new technologies to continue to reduce the cost of goods, which is very important for cell therapy to become mainstay.
Lastly, we're spending on and starting on a long journey to integrate all our ECC systems and make sure our data infrastructure is there as we almost double the size of this company. Where will future CapEx go? We announced a couple of days ago our ADC facility, our end-to-end ADC facility in Singapore... We chose Singapore after a lot of diligence in a lot of different countries and locations, and so forth. One, obviously, for the talent, but also because of the economic relationship that we struck with the collaboration that we struck with the government over there. ADCs are very complex manufacturing. There is not enough CDMO capacity for the ADCs that we have in our pipeline. We have six ADCs, as you heard, fully owned, in-house developed, and we expect a lot of demand from this.
This will be a facility that will be an end-to-end, given the containment and other steps that are required for this complex manufacturing. The second one is cell therapy, and again, we will invest in further sites in cell therapy as our portfolio continues to de-risk. Same with radiopharmaceuticals. With Fusion, we do get a facility and good capabilities, but again, as that portfolio progresses and de-risks, we will make appropriate investments. The end goal here is to have resilient supply chain and to have a data infrastructure that can support our growth for years to come. We're on track to have a mid-thirties core operating profit by 2026. You can see that our operating profit has continued to improve over the last several years.
We've been consistently saying that our R&D expense we expect to remain in the low 20s% of total revenue. As our top line grows, that gives us capacity to make additional R&D investment from a dollar standpoint in all the exciting new studies that you heard about today. Our core SG&A, as a percentage of total revenue, will continue to decline. That'll be driven by the specialty mix that we see. It'll be driven by... You saw the lung map, and the breast cancer map, and the cardiovascular portfolio. Again, leveraging areas that we're already in and optimizing that footprint. Optimizing our global footprint. Again, many of the countries that we're present in today, we don't have the full portfolio of products that we sell there.
So again, as we sell more, you don't need to add, in each of those countries, a whole new infrastructure. And then some of the LOEs that'll come between now and 2030 will enable us to deploy our resources differently. Our core operating profit margin beyond 2026. Again, investment in innovation will drive the growth beyond 2030. So between 2026 and 2030, we expect our core operating profit to remain at at least mid-30s. That's the minimum, or that's the floor that we have set for ourselves. How it evolves from that floor upwards will depend on how our portfolio evolves, will depend on the success that we have, whether it's in specialty areas, in oncology, in some of the primary care medicines, in GLP-1, et cetera, et cetera. It'll also depend on where we continue to see growth.
As you've seen, we've seen very strong growth in emerging medicines and in emerging markets. It'll also depend on how aggressively we invest in new modalities, again, to continue to drive that growth beyond 2030. We do expect that our R&D will remain in that low 20s% through the time period through 2030. So I truly believe that the best of AstraZeneca is yet to come. The next decade will be defining for us, as well as for the industry. Why is AstraZeneca a great place to invest? First and foremost, our therapy area leadership. What does that mean? That means that by 2030, we expect to be number one, two, or three in the therapy areas that we've defined: cardiovascular medicines, respiratory and immunology, oncology, and rare diseases. How will we get there?
The 20 new NMEs that we expect to launch by 2030, the 25 potential blockbusters that we expect to have by 2030, and leverage this breadth and depth that we have across all these therapy areas and continue to grow globally across geographies. Second, continue to lead in scientific innovation. I'm sure you, you felt the energy and the excitement around science in this room, and you felt that as you took the tour of the DISC today. We will continue to lead in new modalities. Science is changing daily, and we expect to be on the forefront of leading that innovation. We will leverage combinations. You heard today from oncology team on replacing first-generation IOs with bispecifics, and replacing radiation with radiopharmaceuticals, and replacing chemotherapy with ADCs, and driving combinations. That is how we'll continue to drive innovation and leverage innovation globally.
We've done partnerships with companies in China. We have a hub in Shanghai for innovation, and again, we will drive innovation globally. Third, financial ambition. This is a company that is not afraid of ambitious targets. $80 billion is a very ambitious target, but it is on a risk-adjusted basis. If you added up all the little boxes that you saw on the right-hand side throughout the presentation, you'd be like: "Well, maybe you're sandbagging, because that number comes to a well, very large number," and it does, but again, this is a risk-adjusted number. We will continue to invest in the next growth beyond 2030. We'll maintain, in parallel, a strong margin and commit to a mid-30s margin. At the same time, we will continue to make, hopefully, smart capital allocation priorities.
Lastly, we will do all of this and decouple that from our carbon footprint. We, again, have very ambitious targets in reducing our Scope 1 and Scope 2 emissions and Scope 3 target. We're leading the industry. I don't think any other pharma company in the world has set these types of ambitious targets. We truly care not only about science, we also care a lot about our planet. This is the only planet we have, and we are science-led, and we're changing the world. I don't think we would achieve any of this without our people. As I've traveled the world, as I've been part of this company for the last three years, I've had the privilege of meeting some really, really amazing people, and it is an incredible privilege to work with all of them.
We have the most brilliant minds, the most passionate people, and these are people who, when they come together, can truly change the world. So with that, I would like to conclude and invite the boss and Susan and Christian, and David to the stage so we can take some questions, and then...
Thank you, Aradhana. So who wants to start? I have a microphone here if someone wants to take it to distribute it to... No, you don't need it? Okay, cool. All right, actually, let's start back to on the left-hand side this time. Sorry, Sachin, we started on the right-hand side this morning.
Thank you, Pascal. It's Matthew Weston from UBS. Two oncology questions, if I can. The first to David: You mentioned in your presentation IRA is coming and the direct impact of the 20% rebate, but there's also the indirect consequences that PBMs are gonna suddenly be responsible for a lot more catastrophic cover. I'd be very interested to understand what you've modeled in terms of additional PBM rebates, step edits, or barriers to therapy that we should assume coming next year. And if you can give any feedback on any early discussions you've had with PBMs, that would be great. And then the second one, a general one for Susan. You've given us some phenomenal detail. You also give us those great tumor maps, which illustrate exactly where you're attacking each of the disease areas.
In those tumor maps, there's actually quite a lot of overlap of multiple modes of action and combinations that are targeting the same patients. How would you encourage us to model that to make sure we don't double count? Do we model the tumor area, and we're kind of agnostic as to how you get there, or you actually think you can go after them with multiple bites of the cherry?
So maybe what we could do, David, I mean, this—the first question is more relevant to oncology, so why don't you cover it? And, Ruud, if you have anything you want to add, please jump in, and then, of course, Susan will cover the second one.
So, Matthew, the first piece that I'd say on this is that I do think that the pressure that PBMs may be under will first have to do with how much their per member per year is adjusted to reflect this new 60%. I think that it's important that all of us recognize that while the premium increase for members or beneficiaries or individuals is capped, that there is a weighted average price on a per member basis that the government pays to the large administrators of the plan, and that number, I think, is gonna go up. How much? We'll see. I don't know. That's got to play itself out, and I think that obviously within that context, it's pretty important to understand how some of the smaller diseases in terms of incidence might get affected.
More specifically then, I think that one of the tools that PBMs have at their disposal is obviously, medicine utilization and step throughs, and you allude to that. We really believe that the best way to defend against that is to make sure that we've got best-in-class medicines and super clinical value propositions. And we've been competing, or at least negotiating, with PBMs who have tried to extract value out of us, since the dawn of time, and so there's no change there. I do think that we've tried to also anticipate that. What have we built in? We're cognizant of the places where we're playing in classes where there are multiple competitors.
And we're cognizant that that means, and I've alluded to that, I've more than alluded to it, I've commented that as we've thought about kind of what we need to do to stay competitive in the BTK space while we wait for the echoes and we wait for the amplifies, is recognize that we probably will have to go through some gross to net pressure in order to maintain our competitiveness. And then I think also there's probably gonna be some added pressure, to your point, that we might face. How have I modeled it? I sorta think that there's probably some general risk of some additional percent that I'm gonna have to manage, but I don't think about it outside of kind of that general term. Ruud, would you add?
There's only one element, and that's applicable, of course, for oncology, but also biopharma, that the out-of-pocket cost will be much lower-
... moving forward. And that means that we assume that patients will stay longer on therapy, abandonment rates will be lower, and especially for more specialty care products, high-priced products, that we're also hoping that we will see less free goods with via our programs. So I think that will be the balance in the end of the day we need to manage. David?
Just Susan, really quickly on this, I mean, I think, Matt, the last piece, and I mentioned this in Q1, we're seeing... and Ruud gets to this. I mean, this is Ruud's point, but we're seeing early signs of improved access as affordability goes down. We're seeing early signs that abandonment is going down. Now, we have to move from early signs to something that we can quantify, but I do think that if we see free goods moving downward, if we see patients coming onto therapy and staying on therapy, the impact that that has for medicines like Tagrisso and medicines like Calquence, with LAURA, long treat to progression time horizons, with Calquence, long treat to progression horizons, it can really have impact. Sorry, Susan.
Maybe just to before you answer-
Yeah
... the second question, Susan, just to add is that I think it's important, Matthew, to keep this also in context. You know, we're almost $50 billion company, I mean, $46 billion last year, but moving into that direction. You look at the growth rate in the first quarter, we are like 15%-16%, and you look at our guidance for this year, and you take, you take 1% of our sales, it's $500 million. So when you try to think about the IRA impact, we never said it would have no impact. It will have an impact. What we're saying is there are ways to manage it, and certainly also consumption should increase because people would have more access and better access.
But then you have also to look at the net impact and put it in the relation to our global sales, and our ability to absorb this, and so possibly have a negative effect on our growth rate, but our growth rate remains very high regardless. There's all these new products, new indications that are coming through that we talked about in the course of the day. Susan?
Okay, so let me try and answer the question in the context of one specific cancer type, and if I haven't answered it, we can come back. So if you take breast cancer, for instance, I'm gonna just give Ingrid Mayer, who leads our breast cancer strategy team, heads up that I'll come to you for some extra color. If you take, you know, the fact that you've got Camizestrant, you've got Truqap, you've got the, you know, both ADCs in HER2 and Dato-DXd, you know, all of them having trials within the ER-positive second-line metastatic breast cancer space, for example. But within that, in terms of the assumptions that we're often making, you've got the endocrine-sensitive disease that you're really targeting with your replacing backbone endocrine therapy with a better endocrine therapy.
As you've seen, actually, most of the Camizestrant development plan is actually focused on the earlier lines than second line, so it's earlier into first line, and then into the adjuvant setting, rather than that second-line setting, where you've got more resistance coming through. But Truqap is focused on that setting, overcoming that endocrine resistance for those patients that have had a trajectory of more endocrine sensitivity. And then the ADCs are focused on where chemotherapy is currently built. And then there's gonna be an overlap, obviously, between the HER2 expressing, particularly at the lower end of HER2 expressing, and the TROP2 expressing. This is why we think that biomarkers are an essential future component of care, 'cause doctors will have individual patients in front of them and want to make a decision about which is the best ADC to use in which context.
So you know, that, you know, that's how we see it. I mean, you can ask David about how we model the sales value. So there is some overlap, but there's also some additivity, because you're expanding some of the duration on therapy, you're expanding the range of patients that can be treated because the safety profiles are a little better. I don't know, Ingrid, do you want to add some color?
Yeah. Thank you, Susan. Hi. So I think to build on that, there's also not overlap, but there's a staggering of different patient populations within the same setting. So cancers are very heterogeneous. The patients that funnel into first-line, second-line, are not, they're not the same. So sometimes when you see several trials within, let's say, first-line breast cancer, where you have SERENA-4, SERENA-6, CAPItello-292, EVOPARA-1, they actually tackle very different patient populations, so they don't overlap at all in that sense. And therefore, while they're all first-line trials, they really are very different proposals because it, it can't be one size fits all. It's all about biomarker, different patients, different needs, and tackling that with the right medication for the right patient at the right time.
Did you want to come back here?
Yeah, this topic seems to generate a lot of interest.
Yeah.
Coming back a moment about the, the IRA and the impact. All the numbers you have seen on the screen have already factored in our internal modeling. Don't double count in a negative way. Everything what you have seen on the screen is already factored in.
Thank you. Oh, Luisa?
Say, Luisa. Yep.
Thank you. Luisa Hector, Bloomberg. Okay, I've got three, sorry, but what do you think or why, why do you think there is a mismatch between your internal budget, your $80 billion, and consensus? Because a lot of the drugs you've told us about today for revenues for tomorrow, we are fairly familiar with those. And where do you see the greatest mismatch? Is it in biopharma? Which therapy areas? Complexity, so $80 billion understandably is going to be a more complex revenue line than today. I'm just curious what you think is the optimal number of therapy areas for a company of your size. Are you there now, and that's it? And then maybe just a quick one on Camizestrant. I think this could be a very important catalyst for next year.
Could you just remind us on the safety profile, anything we should be looking out for or where you think you may be differentiated? Thank you.
So let me try, and, and Aradhana please, jump in, and I guess Susan, you could cover or Christian could cover the Camizestrant question. And by the way, if anybody wants to jump in also on this mismatch question. I think it's, it's left us a little bit perplexed for a little while, actually, I have to say. And my sense is, for a long time everybody was so focused on Dato and a couple of events that, people stopped looking at the rest. And it's only more recently that, at least from our where we, stand, we've had the impression, you guys in the market as a whole started looking at the rest of our pipeline.
It's not surprising because, you know, there was so much excitement about the ADC, and the rest of the pipeline was progressing, but, you know, it was not so visible. I think that's one reason for the overall mismatch. And then, you know, I think try to understand the value of this product takes a lot of time. I think one of you in the room told us that it took him two months of intensive work to go through the pipeline, and David actually said it. I mean, you're gonna have to forecast at least in oncology, eight NMEs, and I cannot do anything for you about this. You got to do it, right?
So we are trying to help you with those pointers to give a sense of the potential, but at the end of the day, the work has to be done. And I think what's important to keep in mind is the breadth of the portfolio is not a weakness, it's a strength. It can be a weakness if we don't know how to manage it, or if we manage it. If we don't manage it very well, of course, it could be a weakness, but it can be a tremendous strength if we actually manage to leverage this wealth we have in the portfolio through better treatment algorithm. You've heard everybody talk about treatment algorithm, whether it's oncology or cardiovascular disease or respiratory disease.
So managing the treatment algorithm and giving a solution to every patient, not every, but almost every patient, a targeted solution. And that will enable us to partner much better with physicians because we actually bring them solutions for their patients across a whole range of disease states, and then it also helps us combine. So of course, it actually requires that we manage that very well, this combination and this treatment algorithm, that's why we have the tumor map. But hopefully, you've seen the tremendous teams that we have across the company in cardiovascular disease, respiratory, immunology, and rare disease, oncology. I think we have the team that will enable us to actually achieve this.
And ultimately, we'll be left with the permanent question in our industry, but also in business in general, is how do we fund all of this? And how do we prioritize, and how do we manage to deliver on our financial goals but still invest in our pipeline? But we've been living through this for the last 10 years, so we'll continue living through it, yeah. So I really think it's this question people come up with complexity is actually a strength if we manage that very well. And if you look at it, and essentially we have oncology, we have a team that manages that, and the mission there, the shared ambition is clear. It's eliminate cancer as a cause of deaths, and that's what everybody comes to work to achieve.
Then we have a biopharmaceutical team that is also focused on, our own goals in cardiovascular, disease, et cetera, and we have a rare disease. So essentially, what you look at a very rich pipeline is fragmented in three parts that everybody manages, you know, I think very well. So that's what I would have to say about this, and-
Christian?
Christian.
Tommy. So, Luisa, let me start. First of all, Sunil mentioned during the presentation, the development of this drug has been incredibly careful. We took the time that was needed. We went very fast, but we took the time. We did the right trials. We characterized very, very well the dose through randomized studies, so we are sure that we have the right dose for metastatic disease in adjuvant setting. And we characterize also the treatment management for some of the adverse event. Now we have hundreds and hundreds of patients enrolled in our programs. SERENA-4, SERENA-6, CAMBRIA-1, CAMBRIA-2, SERENA-2, all ongoing, some already complete enrollments. We know very well what are the adverse event. Let me start what we do not see. We do not see GI toxicity.
Very important because this is what is bothering with the other third, most of the patients, nausea, some vomiting, we have very, very little, none. The two main adverse events that we are observing are some pulse rate going down, bradycardia, completely asymptomatic. That is something that the patient fundamentally does not even realize that they have. And visual disturbances that are very, very light, very mild in grades, is a kind of adjusting from the changing light between day and night. The patient, after some days, get used to this, I can manage. That doesn't impair at all the daily living, driving or doing the thing. So we believe that this drug has definitely the right profile in to fit not only the metastatic setting, but also the adjuvant.
I think the excitement that there is out there, because it's driven not only... You know, when you have such a large program like we do, and you are enrolling ahead of schedule, means that they like the drug and the patients stay on. So we are pretty pleased with the safety profile of the drug.
Can I maybe make last comment? Because this question about complexity, et cetera, comes regularly, actually. But one last point about the power of combinations. You know, there are lots of ADCs, but when we have data, for instance, combining dato with Tagrisso, if what it's combinable, if they see it, nobody else does that. And then people can't say a TROP2 is a TROP2 is a TROP2. That's not true. They are not the same. And then even if they are the same, until you have the combination data, you cannot prove it. And we've seen it time and time again in the history of the industry, when you combine products and you deliver a superior outcome, all competitors need this combination data to compete.
And so it's true across the entire portfolio in oral GLP-1, if we have data in combination with our PCSK9, in combination with baxdrostat, or in combination with Farxiga, another oral GLP-1 will have to have this data. And that really creates a barrier to competitors that is actually quite formidable. Again, we have to execute to hang on this, but if it works, it will be a tremendous differentiation.
I've got a mic, so I'll go. Emmanuel Papadakis at DB, thanks for taking the questions. One on dato. Susan, thanks for reminding us the solid benefit you showed in the non-squamous subgroup. Have you got any rationale yet to explain the detriment you showed in the squamous subgroup? And when are we going to see some biomarker data to help enhance confidence on the probability of success in Avanzar next year? Saruparib, little surprised you've still not initiated anything yet in ovarian, which would have been the common sense, perhaps lead indication, given olaparib's clinical development. So any update there, and have you made the decision now to definitively develop it independently? And then I'll take that dividend question. You outlined a high single-digit minimum growth outlook for the rest of the decade.
Is there any reason why a progressive dividend policy wouldn't match that at a minimum? Are there any drags such as CapEx, business development, et cetera, that might work against it? Thank you.
You have to... The dividend question, I will start with the Dato question. Is that okay, maybe, Leora, you take that one? You know the field very well.
We have ongoing work from TROPION-Lung01 that has really helped us explain the difference in the benefit that we see in squamous and non-squamous, and we'll be disclosing the biomarker data in the next 12 months, and that is incorporated into the work that's going on with Vonzar as well as TROPION-Lung10.
Just to add, in terms of, you know, what Matt showed you, is that, with the QCS biomarker, what we have seen is a difference in the, in the biomarker prevalence by histology. Not just in the trials that we've got with dato, but also in other trials that we've looked at, that that is, you know, a relatively consistent finding. So I think that's one part of the explanation about those, the relative difference between non-squamous and squamous that was observed in TROPION-Lung01. I think the other factor is, of course, we did see, severe ILD events in the, in the arm. There was a little imbalance between squamous and non-squamous, probably because the squamous patients tend to be heavier smokers.
There tend to be a higher prevalence of that, and so they've got a higher predisposition to ILD events within that. And then also the relative sensitivity to the chemotherapy may be different. So I think the answer is, it's a combination of reasons why that is the case, but I think prevalence of the biomarker is one part of that piece as well.
You asked specifically on Avanzar. We are de-risking Avanzar because, of course, we will make the focus of the readout on non-squamous. And then, of course, we will analyze the squamous histology as well, because we are all also the patient. So this is the way also we are de-risking Avanzar.
I would like to just maybe take one minute before we get back to Tezspire also. You know, Pascal just made a point on, well, my words, not Pascal's, but the ADCs are not an ADC are not an ADC. We can't just assume because the target is the same, that necessarily the medicine is gonna perform the same way, and I think there's lots of reasons that sit behind this. I think that actually it's very interesting to take a look at some of the lung cancer histology, both statements that have been made and data that we're seeing, to help underscore the fact that I actually think that there's a lot more to understanding the efficacy and the safety that sits behind these medicines that may cause them to be differentiated.
What might be true of what we're understanding about Dato through the QCS work may not necessarily be applicable to all TROP2 ADCs, just one element of thought.
... So to answer your question about Saruparib, so we are excited about the potential for Saruparib. You know, the—as you've seen, the trials that we've currently got going are going into places that are different from where there are current indications with Lynparza. What we're doing is taking the learnings that we've had about PARP sensitivity and translating that into a development program, which, which I think has got great potential by going into earlier lines and other settings. Now, of course, in the earliest line of ovarian cancer, you've got a very high bar with what we've got with olaparib in that context. And you also see that we've got the ambition in that disease to transform it with ADCs, with our folate receptor alpha ADC, for example.
So I think there is a strategy with ovarian cancer. You will see further trials with Saruparib that will be coming through, and it's actually quite a large portfolio of trials across multiple different indications. And, you know, in terms of the partnership that you alluded to, I think we're just gonna stick with what we've said before. We are minded to partner with a very good collaboration that we've already established on Lynparza.
You had to have the dividend question as well.
Yeah, sure. So today, we set our ambition for 2030. We set our revenue ambition, we set the ambition for profit, and the next step is actually to execute on that ambition. There are obviously a lot of variables that'll happen between now and 2030. There'll be hopefully a lot of de-risking, but there's so many elements that'll change between now and 2030, whether it's our own programs, competition, world events, and so on and so forth. So we cannot commit to a dividend between now and 2030, and that's a decision, again, that the board makes, looks at all capital allocation priorities and how we're progressing towards our goal, and we'll make a decision as time goes on.
Sachin, Sachin, wait, let's go back to the right-hand side for one or two questions.
Sachin got six questions today.
Sachin Jain, Bank of America. I'm gonna keep it to a couple, if I may. So firstly, just a commercial. You've talked about $20 billion peak sales for 2024, 2025 rates. Just a provocative question for you, David: Given the potential for Imfinzi uplift, why isn't Avanzar up to half of that $20 billion opportunity, given it's a first-line all-comer study? And then the second one is for Aradhana. To stay mid-thirties margins with R&D in the low twenties implies about $4 billion, I think, of incremental SG&A spend. A, would you agree with that? And B, if you could just frame how much of that is gonna be for the biopharma, obesity PCSK9 build-out. Just, I think that's important for investors to understand the upfront investment versus long-term peak sales. Thanks.
So, Sachin, I want to make sure that I've got your question. I think you're being a tad cheeky with me on, but I appreciate. So this is a what's Avanzar as part of the Imfinzi ambition?
It was the Avanzar peak sales discussion in the Imfinzi uplift. So, say, just framing the size that relates to the $20 billion.
Got it. Okay, thanks. Well, I mean, look, I think that if we just simply... Before getting to the Imfinzi part, if we just simply look at dato, and I think that Susan showed this quite clearly on the slide in terms of the number of frontline lung cancer patients that are being treated with chemotherapy in combination, with PD-1 or with PD-L1, it's a significant number. And so to my mind, actually, we take a look at, and this kind of gets to the point that Ingrid was making in breast cancer, but I look at OS TL07, TL08, and Avanzar from a dato perspective altogether as a very significant part of how we think about that $5 billion+ that we've got on with dato.
There's a couple of variables that I think are gonna come to play with respect to how much Imfinzi uplift we're gonna get. I think the timing of Avanzar relative to '07 is gonna be important, and I think that how we're able to advance the biomarker work is also gonna be important to the degree that we're able to have that be a part of what we promote in an Imfinzi label. I think will play into it. So I would say that today, we have to acknowledge that Imfinzi is not the leading PD-1, PD-L1 in combination with chemotherapy today in frontline lung cancer.
But I think that there is a nice opportunity to be able to see how it can grow within this and probably could be a benefit to the upside relative to some of the things we're talking about here.
Then... Oh, do you want?
Yeah.
Do you want me to address?
Oh, yeah, yeah. Sorry.
So I think on your margin question, so again, we've said consistently we'll be in the low 20s, so let's say 21%, you know, of total revenue. Of course, we expect total revenue to grow, given the ambition we've set. So I think that gives enough room for R&D. Obviously, none of the R&D colleagues will agree with me that there's ever enough budget, but that's the ambition. And then on SG&A, I think again, it's hard to sort of be explicit because it's very dynamic, right? As we launch more products in lung cancer or breast cancer, where again, we already have presence versus in perhaps new oncology areas where we need to build. For example, when we launched Himalaya and Topaz, we had to build in GI, where we were not already present, right?
So hopefully, we get leverage, operating leverage from areas we're already present in. Similarly, as Farxiga hits LOE in the US, again, we do expect that ex-US, where a lot of the business in Farxiga is, that that portion remains, right? Farxiga may fall off a cliff in the US, but that will not be necessarily the case in emerging markets. And again, as time goes on, the support required for that is much less. The brand value is much more. I mean, Crestor is still a billion-dollar product. So again, we'll need to be dynamic on how we invest.
Then if the oral GLP-1, which again is early, but if we start seeing signs of success and how that progresses, we may again look to dynamically shift how we invest the sales and marketing resources and build, build in that area appropriately. The DAPA combinations, I think, are very unique because they're very discrete areas. They're almost specialty areas in and, in and of itself, right? High proteinuria, the 10% of CKD population, that's a very different sales force versus, you know, a huge primary care sales force. So again, we'll need to shift that dynamically. Ruud or David, you wanna comment on that or no?
No, I think you have explained it very well.
Yeah. I think the important point also is, as Aradhana was saying, is you to think about it over time, right? Is that, in most parts of the world, outside the US, we will have Farxiga for a long time, so we will shift, as she explained, to Baxdrostat, to the combinations, to the PCSK9 over time, right? So it's not like a company that doesn't have the infrastructure in primary care. I've lived through this, in the past. If you don't have the primary care structure, it's very hard to build it, not only operationally, but mostly financially, 'cause your P&L doesn't allow you to carry this. But if you have it, you can actually shift it.
In the US, we have to recognize we have a gap, but we, because we lose Farxiga, late 2025, but hopefully, we have Baxdrostat launching and other products, and then we'll be able to bridge to, the old PCSK9 and the GLP-1, et cetera.
One other element which I think will help on SGNA is the respiratory portfolio, right? And that is, you know, again, most of the Airsupra we just launched, Breztri's been a few years back. So that is still you know, Fasenra, Tezspire, all early in their journeys. And again, it requires a lot of primary care investment, and it's probably, you know, three to four years before it starts breaking even. But once it starts breaking even, then you can see much more sort of profitability coming from those drugs.
Maybe here first, and then Matthias.
Hi, thanks. Emily Field from Barclays. The first one, I guess, is a bit cheeky, but growth seems on track for, you know, through the end of this decade, and not to jump too far ahead, but you also talk about sustained growth post-2030. You know, and after 2030, you will be facing some additional major LOEs to Tagrisso and Imfinzi and Calquence. So, you know, when you mention sustained growth post-2030, do you expect to grow through those LOEs? And then the second one is, Susan, you kind of touched on this in one of your earlier answers, but, you know, it seems like we're gonna be getting some really exciting data from DESTINY Breast 06 and the HR-positive HER2-low space. So why stop there and not continue to go further earlier on in the treatment paradigm?
I know you, you're very excited about the SERD, but I was just wondering if you could provide some more detail on that.
Susan, do you want to start with this one?
Well, again, I can start, Ingrid. Feel free to jump in if you want. But basically, again, it's about this, you know, first-line ER-positive breast cancer is not monolithic. It is a heterogeneous patient population. You've got patients that are endocrine sensitive, and you've got patients that have lost their endocrine sensitivity. I think for many patients that are endocrine sensitive, again, they've got a range of other comorbidities and a range of ages. You know, your, you know, your eighty-five-year-old grandmother might not want to be going onto an IV treatment every three weeks and may prefer to have an endocrine treatment-based treatment. And it, you know, with long histories and a long trajectory, there's gonna be a difference in that patient population.
So I do think over time, you're gonna have a segmentation, even at first line, and identify those rapid progressors that have progressed within 6-12 months of an adjuvant treatment, for example, that actually have different biology. And they, you know, if you get great results with a ADC, they may... Some of those may go on to ADCs, but there's going to be heterogeneity of choice, and it's not going to be universal in that context. Ingrid ?
Not much to add to that. Like, it's what Susan said, is essentially in first-line, you have most cancers being very, very dependent on hormonal treatment, and a minority need something like cytotoxic treatment, where an ADC like Enhertu would do well. So while it makes sense to bring it earlier, it's a very bespoke patient population who would likely benefit from that, and the majority will really benefit from endocrine therapy, where camizestrant is poised to shine.
I may just add one thing. So we have DESTINY Breast 15, which is a study that's underway, which is answering two important questions. One is, Susan, to your point about those fast-progressing patients, who are patients who have had adjuvant therapy and progressing really fast, and then also includes a cohort of patients who are truly IHC zero, where by IHC definition, there is no expression, at least as noted on IHC test, to try and further go down, how low can we go? I think that's gonna be an important study, and that's now on ct.gov.
Maybe, Sunil, you could say here for the first question. Actually, the first question, I think if I understood it correctly, can we go through the next generation of patent expiries, right? And the ambition, our ambition is to do exactly this, and the reason we believe we can do it is, number one, the new technologies, new products we've talked about. Number two, if you look at Imfinzi, an antibody like this doesn't collapse. It declines over time, and in any case will be replaced with the next generation, bispecific antibodies. And then you are left with Calquence and Tagrisso, which indeed will be affected. But again, in many parts of the world, you can continue competing.
I think there was one thing on your slide that didn't get mentioned, that it's a small molecule, L858R-
Yeah
... combination that potentially could be a fixed combo to Tagrisso. Do you want to say a few words about this one?
Yeah. You know, as has been noted in all the presentations today, I think having a lung cancer ambition, a breast cancer ambition, allows us to transition when we're expecting those LOE changes, because we know the clinical community, we know the decision-making, we know where the unmet need is. So for L858R, our patients who may not derive as great a benefit with current third-generation TKIs, including osimertinib, and we recognize that was a big need. So we and through our collaborations with innovation that's happening in China, have addressed L858R, potentially oral formulation, to anticipate that that's gonna be an unmet need, and to bring that drug in combination with Tagrisso, and I think gives us an opportunity for LOE beyond LOE with Tagrisso.
And I think that's the kind of mindset that we're bringing across our portfolio. And again, that happens because we know the disease setting so very well.
It's a substantial proportion of the EGFR population, actually.
Yeah, up to 40%.
Up to 40% we could address with this fixed combo.
I think at a thematic, kinda larger thematic level, and just building on what Pascal and Sunil have said, if we think about just Tagrisso in general, I think that thematically, how can Tagrisso become now a backbone for EGFR treatment? You've got the Dato frontline, you've got Dato second line, we've got the ability to think about... We talked about the EGFR c-Met ADC, what that can start to look like. There'll be other ADCs that are not ours, that other companies are gonna wanna put on top of an Osi backbone. And then you've got the L858R that we just spoke to. And I think that the work we've done with FLAURA2 opens up remarkably the opportunity to do this.
So FLAURA2 is not just a defensive strategy against how we think about competitors coming into the space with combinations, but FLAURA2 is a proof point, together with ORCHARD, two really important sets of studies that allow us to think about how we extend that out. And I'd hope that Anas convinced you that we've got a lot in hematology beyond Calquence.
Thanks, David. So we take one last question on the left. Yeah.
Oh, thank you. I'm Matthias Häggblom from Handelsbanken, and I squeeze in two, please. So the $1.5 billion investment into ADC manufacturing in Singapore per announcement yesterday, should that be viewed as a sign of confidence in an internal ADC pipeline passing through some kind of threshold? Or is it rather that lead times are so long in this complex manufacturing that as a consequence, you need to take decisions early? And then secondly, some of us gathered in New York 11 years ago at the most recent Investor Day. I hope it's not 11 years to the next one. But I'm curious to hear from you, Pascal, what in particular has changed most with the company you lead today, in contrast to the company you then just took over leadership for? Thanks so much.
So the answer to the first question is yes. It is driven by the confidence that we have on our internal ADCs. It is also because, like I said, we have a very attractive economic partnership with the Singapore EDB. So just suffice it to say, the $1.5 billion is a headline number. And thirdly, that is an investment over a several-year time period, right? It's not all in one year. It's gonna be a multi-year project. And that's actually the case with all our CapEx projects. They're all multi-year projects.
I'd just say that there are some countries like Singapore in the world, that know how to make it attractive to invest in their country.
That's right.
And the other thing is that, you know, we've learned over the last few years with, with, on HER2, and more recently, dato, that there is a limited capacity, CMO capacity, in the world for, for ADCs. And if we want to be a leader in ADC, we have to be able to manufacture, at capacity and be, and, you know, and be able to operate on our own. The last question you have is a really good question because it actually is a good conclusion. I often remember this, and actually, we were talking about it with Rod a few minutes ago. I remember about the first investor we organized a number of years ago and today.
Of course, we could talk about all the technologies, the products, but hopefully, what you noticed today is the amazing strengths of the team we have. You know, make me so happy to see how many people, how many talented people we have around the organization. It is so rewarding, and you can see that we actually all work together very, in a very good manner, a very collaborative manner, and making a huge difference to patients, but also to the company. So that, for me, is the biggest difference. The next part of our journey, next step of our journey to 2030 and beyond, is an ambitious one, no question.
But hopefully, you saw that we have what it takes from a product technology viewpoint, and, and, and importantly, we also have it in terms of the team that is gonna manage those assets and those technologies. And I hope now we'll find the money to finance it all. All right. Thank you so much. So let me just conclude with a few slides. One slide, actually. We want to keep on time, so I'll just quickly, you know, repeat some of the things you said, and I, that I just said. Actually, you know, our ambition is really to achieve $80 billion by 2030. But importantly, our ambition is to continue growing past 2030, what internally we've been calling the day after tomorrow.
That's the most challenging aspect of our jobs, but also the most exciting, is actually to manage not only today, tomorrow, but also the long term. It's challenging because we have to deploy our resources in a balanced manner, so we don't focus every effort on our near to mid-term. It's also very exciting because this industry is one of the best places to be in. Innovation is so enormous everywhere that it really keeps everybody excited every day coming to work to leverage this innovation to the benefit of patients. I want to repeat that we have this commitment to our core operating margin improvement beyond 2026.
Of course, as I said this morning, it will be influenced by how much value creation do we have in our hands by 2026, and how much growth can we generate over the next period of time after 2026. Really reminding you that our global footprint is clearly a differentiator. The world is changing. A lot of countries in the world are emerging, who in the past could not afford our products and are starting to afford our products, even in oncology or in rare diseases. And like everybody else, they are aging, and their healthcare needs are improving, and they are expecting us to bring them medicines that will help treat the conditions they are faced with. And having a team that can cover the world is a great advantage, I believe.
We have an amazing late-stage pipeline with $20 billion of potential revenue on a non-risk-adjusted basis from 2024-2025, based on the launches and the readouts that you will actually see unfold over the next 18 months, really until the end of 2025. So again, repeat the message I left you this morning with, which is by the end of 2025, you will have a very good idea of the direction of travel, where ourselves are, and where our pipeline is, and that will give you a very good indication of our chances to get to this goal of $80 billion by 2030. Finally, we are investing in disruptive technologies.
Hopefully, we showed you the progress we're making in some of those, and they're very, very exciting. I think we have an opportunity to really shape the future of medicine, not only in cancer, but also in rare diseases, cardiovascular disease, immunology, rare, and respiratory diseases. Finally, hopefully, again, you will agree with me, we have the team that can actually deliver this. So thank you so much for your attention today, and thank you so much for your confidence in us and your continuous support as shareholders and analysts. Thank you so much.