AstraZeneca Q4 2025 AstraZeneca PLC Earnings Call | AllMind AI Earnings | AllMind AI
Q4 2025 AstraZeneca PLC Earnings Call
Speaker #2: Good morning to those joining from the UK and the US. Good afternoon to those in Central Europe, and good evening to those listening in Asia.
[Company Representative] (AstraZeneca): Good morning to those joining from the UK and the US. Good afternoon to those in Central Europe, and good evening to those listening in Asia. Welcome, ladies and gentlemen, to AstraZeneca's full-year and Q4 2025 results conference call 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.
[Company Representative] (AstraZeneca): Good morning to those joining from the UK and the US. Good afternoon to those in Central Europe, and good evening to those listening in Asia. Welcome, ladies and gentlemen, to AstraZeneca's full-year and Q4 2025 results conference call 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.
Speaker #2: Welcome, ladies and gentlemen, to AstraZeneca's full year and Q4 2025 results conference call for investors and analysts. Before I hand over to AstraZeneca, I'd like to read the safe harbor statement.
Speaker #2: 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.
Speaker #2: 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.
Speaker #2: 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.
[Company Representative] (AstraZeneca): 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 meeting. For those joining remotely, 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 at any time during the call. For those attending in person, roving microphones will be available to ask questions during the Q&A. After the presentation, you'll be invited to raise your hand in the air, and we will bring the microphone to you. When you receive the microphone, please state your name and organization. I must advise you that this presentation is being recorded today. With that, I will now hand you over to the company.
[Company Representative] (AstraZeneca): 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 meeting. For those joining remotely, 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 at any time during the call. For those attending in person, roving microphones will be available to ask questions during the Q&A. After the presentation, you'll be invited to raise your hand in the air, and we will bring the microphone to you. When you receive the microphone, please state your name and organization. I must advise you that this presentation is being recorded today. With that, I will now hand you over to the company.
Speaker #2: Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this meeting. For those joining remotely, there will be an opportunity to ask questions after today's presentations.
Speaker #2: Please use the 'raise a hand' feature to indicate you wish to ask a question at any time during the call. For those attending in person, roving microphones will be available for questions during the Q&A.
Speaker #2: After the presentation, you'll be invited to raise your hand in the air, and we will bring the microphone to you. When you receive the microphone, please state your name and organization.
Speaker #2: I must advise you that this presentation is being recorded today. And with that, I will now hand you over to the
Speaker #2: company.
Speaker #3: All right. A
Andy Barnett: Right. A warm welcome, everybody, to AstraZeneca's full-year and fourth quarter 2025 presentation conference call and webcast for investors and analysts. I'm Andy Barnett, Head of Investor Relations. Before I hand over to Pascal and the rest of the executive team, I'd like to cover some housekeeping items. Firstly, all the materials presented today are already available on the AstraZeneca investor relations website. Next slide, please. This slide contains our forward-looking statements, including the Safe Harbor provisions, which I'd encourage you to take the time to read. We were making comments on our performance using constant exchange rates, or CER, core financial numbers, and other non-GAAP measures. Non-GAAP to GAAP reconciliation is contained within the results announcements, and all numbers quoted today are in millions of US dollars unless stated otherwise. Next slide, please. Here's the agenda for today's call.
Andy Barnett: Right. A warm welcome, everybody, to AstraZeneca's full-year and fourth quarter 2025 presentation conference call and webcast for investors and analysts. I'm Andy Barnett, Head of Investor Relations. Before I hand over to Pascal and the rest of the executive team, I'd like to cover some housekeeping items. Firstly, all the materials presented today are already available on the AstraZeneca investor relations website. Next slide, please. This slide contains our forward-looking statements, including the Safe Harbor provisions, which I'd encourage you to take the time to read. We were making comments on our performance using constant exchange rates, or CER, core financial numbers, and other non-GAAP measures. Non-GAAP to GAAP reconciliation is contained within the results announcements, and all numbers quoted today are in millions of US dollars unless stated otherwise. Next slide, please. Here's the agenda for today's call.
Speaker #3: Warm welcome, everybody, to AstraZeneca's full 2025 presentation conference call and webcast for investors and analysts. I'm Andy Barnett, Head of Investor Relations. And before I hand over to Pascal and the rest of the executive team, I'd like to cover some housekeeping items.
Speaker #3: Firstly, all the materials presented today are already available on the AstraZeneca Investor Relations website. Next slide, please. This slide contains our forward-looking statements, including the safe harbor provisions, which I'd encourage you to take the time to read.
Speaker #3: We will be making comments on our performance using constant exchange rates, or CER, core financial numbers, and other non-GAAP measures. A non-GAAP to GAAP reconciliation is contained within the results announcements, and all numbers quoted today are in millions of US dollars unless stated otherwise.
Speaker #3: Next slide, please. Here’s the agenda for today’s call. Following our prepared remarks, as usual, we’ll open the line for questions, and we will try to address as many questions as we can during the allocated time. Please limit the number of questions you ask to allow others a fair chance to participate.
Andy Barnett: Following up a pair of remarks, as usual, we'll open the line for questions. We will try and address as many questions as we can during the allocated time, although please limit the number of questions you ask so to allow others a fair chance to participate. We do have a hard stop today at quarter past the hour, as many of us have to catch flights in order to participate in the full-year roadshow. So we will need to cut it short. We'll try and get to as many people as we can. Hopefully, everybody gets a fair chance to ask a question. And with that, Pascal, great year. Over to you.
Andy Barnett: Following up a pair of remarks, as usual, we'll open the line for questions. We will try and address as many questions as we can during the allocated time, although please limit the number of questions you ask so to allow others a fair chance to participate. We do have a hard stop today at quarter past the hour, as many of us have to catch flights in order to participate in the full-year roadshow. So we will need to cut it short. We'll try and get to as many people as we can. Hopefully, everybody gets a fair chance to ask a question. And with that, Pascal, great year. Over to you.
Speaker #3: We do have a hard stop today at quarter past the hour, as many of us have to catch flights in order to participate in the full-year roadshow.
Speaker #3: So, we will need to cut it short. We'll try and get to as many people as we can. Hopefully, everybody gets a fair chance to ask a question.
Speaker #3: And with that, Pascal, great year. Over to you.
Speaker #3: you. Thank you,
Pascal Soriot: Thank you, Andy. Welcome, everyone. It's really a great pleasure to see you all again and to present our full-year results. It's been a great year. Our company, if we can move to the next slide, our company delivered very strong performance both on the financial and, most importantly, the pipeline front. On the financial side, revenue grew 8%, and product revenue, importantly, grew 10%, driven by continued global demand for our innovative medicines. Our core EPS, as you can see here, grew by 11%. We had 16 blockbuster medicines in 2025, with 17 of those growing at double digits with 17 medicines, sorry, growing at double digits. And we have the potential to get to 25 blockbusters by 2030. Remember, when we announced our $80 billion target back in May 2024, we had 12 blockbusters at the time. We now have 16, and we hope to get 25.
Pascal Soriot: Thank you, Andy. Welcome, everyone. It's really a great pleasure to see you all again and to present our full-year results. It's been a great year. Our company, if we can move to the next slide, our company delivered very strong performance both on the financial and, most importantly, the pipeline front. On the financial side, revenue grew 8%, and product revenue, importantly, grew 10%, driven by continued global demand for our innovative medicines. Our core EPS, as you can see here, grew by 11%. We had 16 blockbuster medicines in 2025, with 17 of those growing at double digits with 17 medicines, sorry, growing at double digits. And we have the potential to get to 25 blockbusters by 2030. Remember, when we announced our $80 billion target back in May 2024, we had 12 blockbusters at the time. We now have 16, and we hope to get 25.
Speaker #4: Andy: Welcome, everyone. It's really a great pleasure to see you all again and to present our full-year results. It's been a great year.
Speaker #4: Our company—if we can move to the next slide—delivered very strong performance, both on the financial and, most importantly, the pipeline front.
Speaker #4: On the financial side, revenue grew 8%. And product revenue, importantly, grew 10%, driven by continued global demand for our innovative medicines. Our core EPS, as you can see here, grew by 11%.
Speaker #4: We had 16 blockbuster medicines in Q4 2025, with 17 of those growing at double digits. Sorry—with 17 medicines growing at double digits. And we have the potential to get to 25 blockbusters by 2030.
Speaker #4: Remember when we announced our $80 billion target back in May 2024? We had 12 blockbusters at the time. We now have 16, and we hope to get to 25.
Speaker #4: And many of those new ones actually are either approved, or soon approved, or in Phase 3. So, good hopes that we will indeed get to 25.
Pascal Soriot: Many of those new ones, actually, are either approved or soon approved or in phase III. So good hopes that we will indeed get to 25. At our full-year results last year, we signaled that we are entering an unprecedented catalyst-rich period for our company. Our R&D teams continue to deliver. We had 16 positive phase III trial readouts in 2025. Together, they have a combined peak sales potential of $10 billion, as you see on this slide. In the last 12 months, we have secured 43 approvals for our medicines across major regions, helping us to sustain growth into 2026.
Pascal Soriot: Many of those new ones, actually, are either approved or soon approved or in phase III. So good hopes that we will indeed get to 25. At our full-year results last year, we signaled that we are entering an unprecedented catalyst-rich period for our company. Our R&D teams continue to deliver. We had 16 positive phase III trial readouts in 2025. Together, they have a combined peak sales potential of $10 billion, as you see on this slide. In the last 12 months, we have secured 43 approvals for our medicines across major regions, helping us to sustain growth into 2026.
Speaker #4: At our full-year results last year, we signaled that we are entering an unprecedented, catalyst-rich period for our company. Our R&D teams continue to deliver.
Speaker #4: We had 16 positive Phase Three trial results in 2025. Together, they have a combined peak-year sales potential of $10 billion, as you see on this slide.
Speaker #4: In the last 12 months, we have secured 43 approvals for our medicines across major regions, helping us to sustain growth into 2026. And it's important also for me to recognize the work everybody's done in the company, as far as the company, to do this in particular.
Pascal Soriot: It's important also for me to recognize the work everybody's done in the company as far as the company to do this, in particular, our global operations colleagues, because each time we launch one product, for them, it's probably 50, 60 launches, so many different SKUs around the world. So everybody's done a tremendous job across the organization. If we move to the next slide, the strength of our portfolio was clear in 2025, and we are now taking significant steps to continue to strengthen our manufacturing and R&D footprints in both the US and China. Together, our global reach and our diverse revenue streams really support our low concentration risk and ensure resilience to regional disruptions. Important to keep in mind, I know a couple of years ago, many questions we were getting were, "Are your pipeline complicated?
Pascal Soriot: It's important also for me to recognize the work everybody's done in the company as far as the company to do this, in particular, our global operations colleagues, because each time we launch one product, for them, it's probably 50, 60 launches, so many different SKUs around the world. So everybody's done a tremendous job across the organization. If we move to the next slide, the strength of our portfolio was clear in 2025, and we are now taking significant steps to continue to strengthen our manufacturing and R&D footprints in both the US and China. Together, our global reach and our diverse revenue streams really support our low concentration risk and ensure resilience to regional disruptions. Important to keep in mind, I know a couple of years ago, many questions we were getting were, "Are your pipeline complicated?
Speaker #4: Our global operations colleagues—because each time we launch one product, for them, it's probably 50, 60 launches—so many different SKUs around the world.
Speaker #4: So, everybody's done a tremendous job across the organization. So, if we move to the next slide, the strengths of our portfolio are really clear in 2025.
Speaker #4: And we are now taking significant steps to continue to strengthen our manufacturing and our R&D footprints in both the US and China. Together, our global reach and our diverse revenue streams really support our low concentration risk and ensure resilience to regional disruptions for them to keep in mind.
Speaker #4: I know a couple of years ago, many questions we were getting were: Are your pipeline complicated? Is it diversified? I struggle to get my head around it.
Pascal Soriot: Is it diversified?" I struggled to get my head around it. I hope today people realize better the value of this diversification. We're now talking about concentration risk. It's great to have one or two big, big products. It makes you very, very profitable and makes you look good. But if you lose one of those, as we've seen happen to some actors in the industry lately, it really becomes very painful very quickly. So this diversification, both product-wise but also geographically, is suddenly becoming more apparent as we drive growth through therapy areas but also through regions. So if you look at this chart, we saw growth across Oncology and R&I, in particular, growing each 17% and 12%, respectively. CVRM, of course, was impacted by the patent expiry of Brilinta and Farxiga in the UK, and there will be more of this, unfortunately, in 2026.
Pascal Soriot: Is it diversified?" I struggled to get my head around it. I hope today people realize better the value of this diversification. We're now talking about concentration risk. It's great to have one or two big, big products. It makes you very, very profitable and makes you look good. But if you lose one of those, as we've seen happen to some actors in the industry lately, it really becomes very painful very quickly. So this diversification, both product-wise but also geographically, is suddenly becoming more apparent as we drive growth through therapy areas but also through regions. So if you look at this chart, we saw growth across Oncology and R&I, in particular, growing each 17% and 12%, respectively. CVRM, of course, was impacted by the patent expiry of Brilinta and Farxiga in the UK, and there will be more of this, unfortunately, in 2026.
Speaker #4: I hope today people realize better the value of this diversification. And we're now talking about concentration risk. It's great to have one or two big, big products.
Speaker #4: It makes you very profitable, and it makes you look good. But if you lose one of those, as we've seen happen to some actors in the industry lately, it really becomes very painful, very quickly.
Speaker #4: So, this diversification—both product-wise, but also geographically—is suddenly becoming more apparent as we drive growth through therapy areas, but also through regions. So, if you look at this chart, we saw growth across Oncology and RNI in particular, growing 17% and 12% respectively.
Speaker #4: CVRM, of course, was impacted by the panel expiry of Brilinta and Farxiga in the UK, and there will be more of this, unfortunately, in 2026.
Speaker #4: Despite this, we still grew 2%. Overall, biopharmaceuticals still grew 6% and represent about 40% of our global sales. Rare disease grew 5%. Despite the impact of biosimilars on Soliris, I would say the transition from Soliris to Ultomiris is not totally finished, but close to being completed.
Pascal Soriot: Despite this, we still grew 2%. Overall, biopharmaceuticals still grew 6% and represent about 40% of our global sales. Rare disease grew 5% despite the impact of biosimilars on Soliris. I would say the transition from Soliris to Ultomiris is not totally finished but close to being completed, and Ultomiris is now growing very nicely. We continue to see increasing demand for medicines across all our regions. Of course, strong growth in the US, 10%. We continue to grow in Europe. But importantly, I think I would like to highlight or attract your attention to the emerging markets outside of China. China still grew 4% despite losing Pulmicort to generics. We still grew 4%, which is quite nice, and we remain the largest pharma company in China. But outside of China, 22%. This part of the world is starting to really play an important role.
Pascal Soriot: Despite this, we still grew 2%. Overall, biopharmaceuticals still grew 6% and represent about 40% of our global sales. Rare disease grew 5% despite the impact of biosimilars on Soliris. I would say the transition from Soliris to Ultomiris is not totally finished but close to being completed, and Ultomiris is now growing very nicely. We continue to see increasing demand for medicines across all our regions. Of course, strong growth in the US, 10%. We continue to grow in Europe. But importantly, I think I would like to highlight or attract your attention to the emerging markets outside of China. China still grew 4% despite losing Pulmicort to generics. We still grew 4%, which is quite nice, and we remain the largest pharma company in China. But outside of China, 22%. This part of the world is starting to really play an important role.
Speaker #4: And Ultomeris is now growing very nicely. We continue to see increasing demand for medicines across all our regions. Of course, strong growth in the US—10%.
Speaker #4: We continue to grow in Europe. But importantly, I think I would like to highlight—or attract your attention to—the emerging markets outside of China.
Speaker #4: China still grew 4%, despite losing Pulmicort 4%, which is quite nice. And we to Generix. Remain the largest pharma—And we still grew—company in China.
Speaker #4: But outside of China, 22%. This part of the world is starting to really play an important role. As I said, Europe, we still grow 7%.
Pascal Soriot: As I said, Europe, we still grow 7%. Next slide, please. Importantly, our momentum through the pipeline continues. We now have more than 100 phase three trials that are ongoing. Think about that. 100 phase three trials. It's an enormous momentum going through the pipeline. And this year, we should have 20 phase three readouts. And those readouts, fingers crossed, of course, if they are positive, they will collectively drive another more than $10 billion of peak revenue. And the pipeline 27 should also, again, deliver a similar number, actually slightly higher, in 2027. Of course, not all, but at least the great majority of these phase three readouts need to be positive. Importantly, you can see that there's a growing number of, let's say, assets, but importantly, an increasing value per indication. As our pipeline grows, we continue to focus and prioritize.
Pascal Soriot: As I said, Europe, we still grow 7%. Next slide, please. Importantly, our momentum through the pipeline continues. We now have more than 100 phase three trials that are ongoing. Think about that. 100 phase three trials. It's an enormous momentum going through the pipeline. And this year, we should have 20 phase three readouts. And those readouts, fingers crossed, of course, if they are positive, they will collectively drive another more than $10 billion of peak revenue. And the pipeline 27 should also, again, deliver a similar number, actually slightly higher, in 2027. Of course, not all, but at least the great majority of these phase three readouts need to be positive. Importantly, you can see that there's a growing number of, let's say, assets, but importantly, an increasing value per indication. As our pipeline grows, we continue to focus and prioritize.
Speaker #4: Next slide, please. Importantly, our momentum through the pipeline continues. We now have more than 100 Phase 3 trials that are ongoing. Think about that.
Speaker #4: One hundred phase three trials. It's an enormous momentum going through the pipeline. And this year, we should have 20 phase three results. And those results—fingers crossed, of course—if they are positive, they will collectively drive another more than $10 billion of peak revenue.
Speaker #4: And the pipeline 27 should also again deliver a similar number, actually slightly higher in 2027. Of course, not all, but at least a great majority of these Phase 3 results need to be positive.
Speaker #4: You can see that there’s a, importantly, a growing number of, let’s say, assets, but importantly, an increasing value per indication. As our pipeline grows, we continue to focus and prioritize and, of course, we prioritize the most valuable projects. And you can see in light pink the average peak year revenue per indication.
Pascal Soriot: Of course, we prioritize the most valuable projects. You can see in light pink the average peak revenue per indication. That reflects the increasing individual value of projects and the continuous effort we make to prioritize, even though we have a lot of projects. Next slide, please. The question is often asked, "Oh, let's be on 2030." We said back in May 2024, and we continue saying the same, "We want to be a growth company until 2030, reach this $80 billion ambition, but also be a growth company post-2030." That is why we need to continue investing in R&D. That is why we need to continue focusing on technologies and new medicines that will actually change the future of medicines and drive our growth post-2030. You can see here the list of the five technologies that we prioritize and decided to invest in.
Pascal Soriot: Of course, we prioritize the most valuable projects. You can see in light pink the average peak revenue per indication. That reflects the increasing individual value of projects and the continuous effort we make to prioritize, even though we have a lot of projects. Next slide, please. The question is often asked, "Oh, let's be on 2030." We said back in May 2024, and we continue saying the same, "We want to be a growth company until 2030, reach this $80 billion ambition, but also be a growth company post-2030." That is why we need to continue investing in R&D. That is why we need to continue focusing on technologies and new medicines that will actually change the future of medicines and drive our growth post-2030. You can see here the list of the five technologies that we prioritize and decided to invest in.
Speaker #4: That reflects the increasing individual value of projects and the continuous effort we make to prioritize, even though we have a lot of projects. Next slide, please.
Speaker #4: So the question is often asked, so let's be on 2013. We said back in May 2024, and we continue saying the same, we want to be a growth company until 2030, reach this $80 billion ambition, but also be a growth company post-2030.
Speaker #4: And that is why we need to continue investing in R&D. That is why we need to continue focusing on actually changing the future of medicines and drive our growth—technologies and new medicines that will be post-2030.
Speaker #4: So, you can see here the list of the five technologies that we prioritize and decided to invest in. And if you look at weight management, cardiovascular risk factors, we now have two products in Phase 3.
Pascal Soriot: And if you look at weight management, cardiovascular risk factors, we now have two products in phase III. Of course, our oral PCSK9, for which we will get data in 2027. But we also announced that we have moved our oral GLP-1 into phase III, and we have a broad set of studies covering diabetes, weight loss in monotherapy, combination products, cardiovascular outcome studies. So we have a very ambitious plan for our oral GLP-1. But beyond this, we're also investing in new products that will actually shape the future of this weight management sector, which is in the initial steps, really. And the future will be made of better convenience, longer duration of action for injectables, moving to weekly to monthly. And some of this will come from the partnership we announced with CSPC recently, but also new mechanisms.
Pascal Soriot: And if you look at weight management, cardiovascular risk factors, we now have two products in phase III. Of course, our oral PCSK9, for which we will get data in 2027. But we also announced that we have moved our oral GLP-1 into phase III, and we have a broad set of studies covering diabetes, weight loss in monotherapy, combination products, cardiovascular outcome studies. So we have a very ambitious plan for our oral GLP-1. But beyond this, we're also investing in new products that will actually shape the future of this weight management sector, which is in the initial steps, really. And the future will be made of better convenience, longer duration of action for injectables, moving to weekly to monthly. And some of this will come from the partnership we announced with CSPC recently, but also new mechanisms.
Speaker #4: Of course, all PCSK9, for which we will get data in 2027. But we also announced that we have moved our oral GLP-1 into phase three, and we have a broad set of studies covering diabetes, weight loss in monotherapy, combination products, cardiovascular outcome studies.
Speaker #4: So, we have a very ambitious plan for our whole GLP-1. But beyond this, we also invest in new products that will actually shape the future of this weight management sector, which is in the initial steps, really.
Speaker #4: And the future will be made of better convenience, longer duration of action for injectables—moving to weekly, to monthly—and some of this will come from the partnership we announced with CSPC recently.
Speaker #4: But also new mechanisms. So we are waiting for data on our GLP-1/glucagon and our amylin product. The GLP-1/glucagon in itself has independent value, but we also will combine it with amylin.
Pascal Soriot: So we are waiting for data on our GLP-1 glucagon and our amylin product. The GLP-1 glucagon in itself has independent value, but we also will combine it with amylin. So we should get data this year. So oral agents, long-acting injectables, new mechanisms helping patients lose more fat and less muscle are the directions we are heading into. Now, if you look at ADC and radioconjugates, we now have 8 ADCs that are ADCs that came out of our own pipeline, our own efforts. Three of those are in Phase III. We will get data in the first half of this year for one of those, as you can see here, AZD0901. And importantly, we have new ones, both as ADCs but also radioconjugates that are moving through early development. We have novel linker combinations, payload combinations. We have dual payload ADC. We have radioligands.
Pascal Soriot: So we are waiting for data on our GLP-1 glucagon and our amylin product. The GLP-1 glucagon in itself has independent value, but we also will combine it with amylin. So we should get data this year. So oral agents, long-acting injectables, new mechanisms helping patients lose more fat and less muscle are the directions we are heading into. Now, if you look at ADC and radioconjugates, we now have 8 ADCs that are ADCs that came out of our own pipeline, our own efforts. Three of those are in Phase III. We will get data in the first half of this year for one of those, as you can see here, AZD0901. And importantly, we have new ones, both as ADCs but also radioconjugates that are moving through early development. We have novel linker combinations, payload combinations. We have dual payload ADC. We have radioligands.
Speaker #4: So we should get data this year. So, oral agents, long-acting injectables, and new mechanisms helping patients lose more fat and less muscle are the directions we are heading into.
Speaker #4: Now, if you look at ADC and radioconjugates, we now have eight ADCs that came out of our own pipeline, our own efforts. Three of those are in Phase 3.
Speaker #4: We will get data in the first half of this year for one of those. As you can see here, Sonivy. And then importantly, we have new ones.
Speaker #4: Both as ADCs, but also radioconjugates that are moving through early development. We have novel linker combinations, piloted-ed combinations. We have dual-piloted ADC.
Speaker #4: We have radioligands, so we continue to build these. That will drive our growth post-2030. We, of course, invest in our next-generation IO by specifics.
Pascal Soriot: So we continue to build this that will drive our growth post-2030. We, of course, invest in our next-generation IO bispecifics, in particular, Rilvegostomig. And we combine those with our ADCs, as we've said in the past. Cell therapy, T-cell engagers. We're making good progress with AZD0120 that has good encouraging data in phase 1 but is entering phase 3 this year. And we are moving as fast as we can to move it into hematology indications but also immunology indications. And we also have very exciting data, early data, for Sirovetamig. And it's also moving into phase 3. And on top of this, we have multiple approaches to CAR-T, not only CAR-T but also allogeneic projects that some of them will be in the clinic this year. And we're working on the in vivo approach, as you know. And then we also have new platforms, TCE platforms.
Pascal Soriot: So we continue to build this that will drive our growth post-2030. We, of course, invest in our next-generation IO bispecifics, in particular, Rilvegostomig. And we combine those with our ADCs, as we've said in the past. Cell therapy, T-cell engagers. We're making good progress with AZD0120 that has good encouraging data in phase 1 but is entering phase 3 this year. And we are moving as fast as we can to move it into hematology indications but also immunology indications. And we also have very exciting data, early data, for Sirovetamig. And it's also moving into phase 3. And on top of this, we have multiple approaches to CAR-T, not only CAR-T but also allogeneic projects that some of them will be in the clinic this year. And we're working on the in vivo approach, as you know. And then we also have new platforms, TCE platforms.
Speaker #4: In particular, rilvigostomig. And we combine those with our ADCs, as we've said in the past. Cell therapy, T-cell engagers. We're making good progress with AZD0120 that has good, encouraging data in phase one, but is entering phase three this year.
Speaker #4: And we are moving as fast as we can to move it into hematology indications, but also immunology indications. And we also have very exciting early data for SUROVATAMIG.
Speaker #4: And it's also moving into phase three. And on top of this, we have multiple approaches to CAR-T—not only CAR-T, but also allogeneic projects, some of which will be in the clinic this year.
Speaker #4: And we're working on the in vivo approach, as you know. And then we also have new platforms, TCE platforms, and finally, we're making progress also in our gene therapy programs.
Pascal Soriot: And finally, we're making progress also in our gene therapy programs. So if we move to the next one, I'll hand over to Hannah. We'll take you through the final slides. Thank you.
Pascal Soriot: And finally, we're making progress also in our gene therapy programs. So if we move to the next one, I'll hand over to Hannah. We'll take you through the final slides. Thank you.
Speaker #4: So, if we move to the next one, I'll hand out to Hanna. We'll take you through the final shows. Thank you.
Speaker #1: Thank you, Pascal. And good afternoon, everyone, and good morning to those up very early to join us. So, as usual, I'll start with our reported P&L.
Aradhana Sarin: Thank you, Pascal. And good afternoon, everyone. And good morning to our colleagues in the US who woke up very early to join us. So as usual, I'll start with our reported P&L. Next slide, please. Total revenue increased 8% in 2025. Product revenue, which consists of product sales and alliance revenue, increased 10% with continued growth across all key regions. Alliance revenue increased by 38%, reflecting increased contribution from our share of profits with partnered products such as Enhertu, Tezspire, and Beyfortus in regions where our partners book product sales. Next slide, please. This is our core P&L. The core gross margin landed at 82% in 2025, in line with expectations set out at the start of the year. Fourth-quarter gross margin reflected the normal seasonal pattern as well as $235 million of royalty buyouts for Saphnelo and Rilvegostomig, which were recorded in the cost of sales.
Aradhana Sarin: Thank you, Pascal. And good afternoon, everyone. And good morning to our colleagues in the US who woke up very early to join us. So as usual, I'll start with our reported P&L. Next slide, please. Total revenue increased 8% in 2025. Product revenue, which consists of product sales and alliance revenue, increased 10% with continued growth across all key regions. Alliance revenue increased by 38%, reflecting increased contribution from our share of profits with partnered products such as Enhertu, Tezspire, and Beyfortus in regions where our partners book product sales. Next slide, please. This is our core P&L. The core gross margin landed at 82% in 2025, in line with expectations set out at the start of the year. Fourth-quarter gross margin reflected the normal seasonal pattern as well as $235 million of royalty buyouts for Saphnelo and Rilvegostomig, which were recorded in the cost of sales.
Speaker #1: Next slide, please. Total revenue increased 8% in 2025. Product revenue, which consists of product sales and alliance revenue, increased 10%. We saw continued growth across all key regions.
Speaker #1: Revenue increased by Alliance 38%, reflecting increased contribution from our share of profits with partnered products such as Inhertu, Tespyre, and Befortis in regions where our partners book product sales.
Speaker #1: Next slide, please. This is our core P&L. The core gross margin landed at 82% in 2025, in line with expectations set out at the start of the year.
Speaker #1: Fourth-quarter gross margin reflected the normal seasonal pattern, as well as $235 million of royalty buyouts for SOFNELO and RILVIGOSTOMIG, which were recorded in the cost of sales.
Speaker #1: Core R&D expenses increased by 12%, reflecting the growing number of investment opportunities in our broad and deep pipeline. At the end of 2025, we had more than 300 active trials, and as Pascal mentioned, more than 100 of these in phase three.
Aradhana Sarin: Core R&D expenses increased by 12%, reflecting the growing number of investment opportunities in our broad and deep pipeline. At the end of 2025, we had more than 300 active trials. As Pascal mentioned, more than 100 of these in phase three. SG&A expenses increased by only 3% in 2025, reflecting continued cost discipline and focus on operating leverage. We continue to streamline our business. As a proportion of total revenue, SG&A expenses decreased from 28% in 2024 to 26% in 2025. Operating profit increased by 9%, with operating leverage continuing to be a key focus for the company. We manage our P&L in totality, enabling flexibility in investment decisions throughout the year. The lower tax rate seen in the fourth quarter reflected release of certain tax provisions taken in prior years. Core EPS increased by 11% in line with our full-year guidance. Next slide, please.
Aradhana Sarin: Core R&D expenses increased by 12%, reflecting the growing number of investment opportunities in our broad and deep pipeline. At the end of 2025, we had more than 300 active trials. As Pascal mentioned, more than 100 of these in phase three. SG&A expenses increased by only 3% in 2025, reflecting continued cost discipline and focus on operating leverage. We continue to streamline our business. As a proportion of total revenue, SG&A expenses decreased from 28% in 2024 to 26% in 2025. Operating profit increased by 9%, with operating leverage continuing to be a key focus for the company. We manage our P&L in totality, enabling flexibility in investment decisions throughout the year. The lower tax rate seen in the fourth quarter reflected release of certain tax provisions taken in prior years. Core EPS increased by 11% in line with our full-year guidance. Next slide, please.
Speaker #1: SG&A expenses increased by only 3% in 2025, reflecting continued cost discipline and focus on operating leverage. We continued to streamline our business, and as a proportion of total revenue, SG&A expenses decreased from 28% in 2024 to 26% in 2025.
Speaker #1: Operating profit increased by 9%, with operating leverage continuing to be a key focus for the company. We manage our P&L in totality, enabling flexibility in investment decisions throughout the year.
Speaker #1: The lower tax rate seen in the fourth quarter reflected release of certain tax provisions taken in prior years. Core EPS increased by 11%, in line with our full-year guidance.
Speaker #1: Next slide, please. We continue to see strong cash flow from operating activities, which increased by 23% to $14.6 billion in 2025. We saw capex increasing by $1.1 billion to $3.3 billion, in line with the expectations set out at the beginning of the year.
Aradhana Sarin: We continue to see strong cash flow from operating activities, which increased by 23% to $14.6 billion in 2025. We saw CapEx increasing by $1.1 billion to $3.3 billion, in line with the expectations set out at the beginning of the year. For 2026, we anticipate CapEx investment to increase by approximately one-third versus 2025 as we expand capacity to support future growth. This includes our recently announced US and China investments and previously announced investments in our ADC facility in Singapore, all of which are multi-year projects. Total deal payments in 2025 amounted to $4.2 billion, of which around $3 billion were payments relating to past deals, and the remaining were payments for deals announced in 2025, such as Eccogene. In 2026, we anticipate success-based milestones and sales payments relating to past deals to total around $2.5 billion. Our capital allocation priorities remain unchanged.
Aradhana Sarin: We continue to see strong cash flow from operating activities, which increased by 23% to $14.6 billion in 2025. We saw CapEx increasing by $1.1 billion to $3.3 billion, in line with the expectations set out at the beginning of the year. For 2026, we anticipate CapEx investment to increase by approximately one-third versus 2025 as we expand capacity to support future growth. This includes our recently announced US and China investments and previously announced investments in our ADC facility in Singapore, all of which are multi-year projects. Total deal payments in 2025 amounted to $4.2 billion, of which around $3 billion were payments relating to past deals, and the remaining were payments for deals announced in 2025, such as Eccogene. In 2026, we anticipate success-based milestones and sales payments relating to past deals to total around $2.5 billion. Our capital allocation priorities remain unchanged.
Speaker #1: For 2026, we anticipate capex investment to increase by approximately one-third versus 2025, as we expand capacity to support future growth. This includes our recently announced US and China investments, and previously announced investments in our ADC facility in Singapore, all of which are multi-year projects.
Speaker #1: Total deal payments in 2025 amounted to $4.2 billion, of which around $3 billion were payments relating to past deals, and the remaining were payments for deals announced in 2025, such as ESO Biotech.
Speaker #1: In 2026, we anticipate success-based milestones and sales payments relating to past deals to total around $2.5 billion. Our capital allocation priorities remain unchanged. We currently have interest-bearing debt of close to $30 billion, which is a level we're comfortable with as we continue making investments to drive future growth, expand our supply chain globally, and further strengthen our R&D pipeline.
Aradhana Sarin: We currently have interest-bearing debt of close to $30 billion, which is a level we're comfortable with as we continue making investments to drive future growth, expand our supply chain globally, and further strengthen our R&D pipeline. Our net debt-to-EBITDA ratio currently sits at 1.2 times. Today, we are pleased to confirm a second interim dividend of $2.17 per share, resulting in a full-year 2025 declared dividend of $3.20 per share. In 2026, we intend to increase the annual declared dividend to $3.30 per share, in line with our progressive dividend policy. Today, we also issue our 2026 guidance. As usual, our full-year guidance is at constant exchange rates. We anticipate total revenue to grow by a mid to high single-digit percentage, driven by strong underlying momentum in the business. The growth will be delivered despite known headwinds in 2026, including VBP in China this quarter for Farxiga, Lynparza, and Roxadustat.
Aradhana Sarin: We currently have interest-bearing debt of close to $30 billion, which is a level we're comfortable with as we continue making investments to drive future growth, expand our supply chain globally, and further strengthen our R&D pipeline. Our net debt-to-EBITDA ratio currently sits at 1.2 times. Today, we are pleased to confirm a second interim dividend of $2.17 per share, resulting in a full-year 2025 declared dividend of $3.20 per share. In 2026, we intend to increase the annual declared dividend to $3.30 per share, in line with our progressive dividend policy. Today, we also issue our 2026 guidance.
Speaker #1: Our net debt-to-EBITDA ratio currently sits at 1.2 times. Today, we are pleased to confirm a second term dividend of $2.17 per share, resulting in a full-year 2025 declared dividend of $3.20 per share in 2026.
Speaker #1: We intend to increase the annual dividend declared to $3.30 per share, in line with our progressive dividend policy. Today, we also issue our $2.30 per share in line with our progressive dividend policy.
Aradhana Sarin: As usual, our full-year guidance is at constant exchange rates. We anticipate total revenue to grow by a mid to high single-digit percentage, driven by strong underlying momentum in the business. The growth will be delivered despite known headwinds in 2026, including VBP in China this quarter for Farxiga, Lynparza, and Roxadustat.
Speaker #1: Today , we also issue our 2026 guidance As . our full usual , year constant guidance is at exchange rates . total anticipate We revenue to grow by a mid to high single percentage , driven by digit strong underlying momentum in the business growth will be delivered .
Speaker #1: known despite headwinds The in 2026 , including VPI in China . This quarter . For for Sega , Lynparza and Roxadustat for Sega will also face loss of exclusivity in the US in .
Aradhana Sarin: Farxiga will also face loss of exclusivity in the US in April. In 2025, US Farxiga generated $1.7 billion or 21% of global revenues, while China represented just under half of emerging markets revenue. In Europe, which accounts for 35% of Farxiga total revenue, patent protections across EU markets extend to 2028. While the MFN deal presents a headwind in 2026, the effect is already factored in our guidance and can be absorbed given our large and growing revenue base. Despite these headwinds, we anticipate a broadly flat to slightly higher core gross margin in 2026, driven by backing out the royalty buyout and product sales mix. We expect a core tax rate between 18% and 22% in 2026 and core EPS growth of low double-digit % at constant exchange rates.
Aradhana Sarin: Farxiga will also face loss of exclusivity in the US in April. In 2025, US Farxiga generated $1.7 billion or 21% of global revenues, while China represented just under half of emerging markets revenue. In Europe, which accounts for 35% of Farxiga total revenue, patent protections across EU markets extend to 2028. While the MFN deal presents a headwind in 2026, the effect is already factored in our guidance and can be absorbed given our large and growing revenue base. Despite these headwinds, we anticipate a broadly flat to slightly higher core gross margin in 2026, driven by backing out the royalty buyout and product sales mix. We expect a core tax rate between 18% and 22% in 2026 and core EPS growth of low double-digit % at constant exchange rates.
Speaker #1: April US for In 2025 , Sega generated 1.7 billion , or 21% of global revenues , while China represented just under half markets emerging of revenue in Europe , which accounts 35% of Patent for markets across revenue .
Speaker #1: EU extended to, while 2028, the MFN deal headwind presents an effect in 2026. The IN is already in. Our factored can be guidance and growing large base.
Speaker #1: We flat to anticipate headwinds, despite given our a broadly slightly gross core margin revenue 2026, driven in royalty buyout and the by product mix sales.
Speaker #1: Expect a core WE tax rate between 18% and 22% in 2026, and core EPS growth double of low-digit percentage at constant exchange rates, based on January exchange rates.
Aradhana Sarin: Based on January average exchange rates, we anticipate a low single-digit positive FX impact on total revenue and neutral impact on core EPS. Next slide, please. As I mentioned earlier, we continue to make significant R&D investments in emerging areas such as ADCs, cell therapy, bispecific, and late-stage CVRM portfolio, which have the potential to drive growth beyond 2030. As a result, we anticipate R&D expenses to be at the upper end of the low 20s % range of total revenue in 2026. SG&A's percentage of total revenue has continued to decline over recent years, reflecting our disciplined approach to efficiency and operating leverage. At the same time, we're making targeted investment to support the next wave of growth with several important NME launches ahead of us, including Baxdrostat, Camizestrant, and Garadacimab, all of which are medicines with blockbuster potential.
Aradhana Sarin: Based on January average exchange rates, we anticipate a low single-digit positive FX impact on total revenue and neutral impact on core EPS. Next slide, please. As I mentioned earlier, we continue to make significant R&D investments in emerging areas such as ADCs, cell therapy, bispecific, and late-stage CVRM portfolio, which have the potential to drive growth beyond 2030. As a result, we anticipate R&D expenses to be at the upper end of the low 20s % range of total revenue in 2026. SG&A's percentage of total revenue has continued to decline over recent years, reflecting our disciplined approach to efficiency and operating leverage. At the same time, we're making targeted investment to support the next wave of growth with several important NME launches ahead of us, including Baxdrostat, Camizestrant, and Garadacimab, all of which are medicines with blockbuster potential.
Speaker #1: average anticipate a low We single digit positive effects impact on total revenue neutral and impact on EPs . slide please . As I mentioned earlier , we to make continue significant R&D emerging investments in such as cell therapy ADCs , , bispecific and late stage CVM portfolio , which have the potential to drive beyond 2030 .
Speaker #1: growth As a anticipate R&D expenses to be at the upper end result , we of the percentage range of low 20s 2026 . total DNA is the percentage of total revenue has decline over recent years , reflecting our efficiency approach to continued and to operating leverage the same .
Speaker #1: At time , we're targeted investments to the making next wave of growth with several enemy important launches ahead of us , percentage Baxdrostat support , Camizestrant and Mab , all of which are including potential .
Aradhana Sarin: While we continue to target a mid-30s operating margin in 2026, our priority remains to drive absolute profit growth and long-term value for our shareholders. As highlighted earlier, we remain comfortable with our current level of gross debt. We anticipate a step-up in core net finance expense for 2026, driven by higher lease expenses and lower interest income. In summary, we saw very strong financial performance in 2025, which we anticipate to continue in 2026. Next slide, please. With that, I will hand over to Dave, who will take you through the commercial performance of our oncology business.
Aradhana Sarin: While we continue to target a mid-30s operating margin in 2026, our priority remains to drive absolute profit growth and long-term value for our shareholders. As highlighted earlier, we remain comfortable with our current level of gross debt. We anticipate a step-up in core net finance expense for 2026, driven by higher lease expenses and lower interest income. In summary, we saw very strong financial performance in 2025, which we anticipate to continue in 2026. Next slide, please. With that, I will hand over to Dave, who will take you through the commercial performance of our oncology business.
Speaker #1: While we continue to blockbuster target a mid 30s operating margin 2026 , our remains to drive absolute profit growth and long priority term value for shareholders .
Speaker #1: As highlighted earlier, we are comfortable with our gross. We remain, we anticipate a level of increase in core net finance expense step up for 2026, driven by higher lease expenses and income.
Speaker #1: and lower we saw In in summary , very interest financial 2025 , which we in anticipate to strong continue in 2026 . Next slide please .
Speaker #1: over to With that , I will hand will Dave , take you commercial through the performance business . oncology of our
Dave Fredrickson: Thank you, Aradhana. Next slide, please. In 2025, oncology delivered total revenues of $25.6 billion, an increase of 14% on the prior year or 17% excluding the 2024 Lynparza sales milestone. Many of our key medicines have surpassed notable multi-blockbuster milestones, with Tagrisso achieving over $7 billion in full-year revenues, Imfinzi over $6 billion, Calquence over $3.5 billion, and Enhertu over $2.5 billion in AZ revenues. This performance is a tangible demonstration of our commitment to bringing medicines with transformative potential to patients globally and is particularly notable given the headwinds from the introduction of the 20% manufacturer's liability under Medicare Part D reform from last year. Turning now to our fourth-quarter performance, total revenues exceeded $7 billion for the first time, up 20% on the year excluding the Lynparza milestone, with all our key medicines in regions demonstrating double-digit growth.
Dave Fredrickson: Thank you, Aradhana. Next slide, please. In 2025, oncology delivered total revenues of $25.6 billion, an increase of 14% on the prior year or 17% excluding the 2024 Lynparza sales milestone. Many of our key medicines have surpassed notable multi-blockbuster milestones, with Tagrisso achieving over $7 billion in full-year revenues, Imfinzi over $6 billion, Calquence over $3.5 billion, and Enhertu over $2.5 billion in AZ revenues. This performance is a tangible demonstration of our commitment to bringing medicines with transformative potential to patients globally and is particularly notable given the headwinds from the introduction of the 20% manufacturer's liability under Medicare Part D reform from last year. Turning now to our fourth-quarter performance, total revenues exceeded $7 billion for the first time, up 20% on the year excluding the Lynparza milestone, with all our key medicines in regions demonstrating double-digit growth.
Speaker #2: Thank you Rodney please slide . . In Next total 2025 oncology delivered revenues of $25.6 billion , an increase of 14% on the prior year or 17% excluding the 2024 Lynparza , sales milestone .
Speaker #2: Many of our key medicines have surpassed notable blockbuster milestones, with Tagrisso achieving over $7 billion in full-year revenues, and Finzi over $6 billion.
Speaker #2: Calquence over 3.5 billion , and in Her2 In over 2.5 billion . revenues . AZ This performance is a demonstration of our commitment to bringing medicines with transformative potential to patients globally , and is tangible particularly notable headwinds from the introduction of the given the 20% manufacturer's liability under Medicare Part D last reform from year .
Speaker #2: Turning to performance, fourth quarter total exceeded $7 billion this time, now to our performance for the first year up. Excluding 20% on the milestone.
Dave Fredrickson: Tagrisso global revenues were up 10%, reflecting continued demand growth across all indications. In the first-line setting, we are now seeing a significant proportion of patients receiving a combination regimen, with FLAURA2 being the clear preference across key markets. In earlier lines, increased adoption of ADAURA and LAURA has been another meaningful source of growth. Imfinzi and Imjudo delivered 37% and 26% growth respectively, reflecting continued demand across tumor types. This growth is broad-based from both continued expansion of newer indications such as ADRIATIC and small-cell lung cancer, and NIAGARA and bladder cancer, as well as increased uptake of more established indications such as HIMALAYA and liver cancer. Calquence total revenues increased 17% in the fourth quarter, driven by additional demand in front-line CLL as we maintain our class leadership position across major markets.
Dave Fredrickson: Tagrisso global revenues were up 10%, reflecting continued demand growth across all indications. In the first-line setting, we are now seeing a significant proportion of patients receiving a combination regimen, with FLAURA2 being the clear preference across key markets. In earlier lines, increased adoption of ADAURA and LAURA has been another meaningful source of growth. Imfinzi and Imjudo delivered 37% and 26% growth respectively, reflecting continued demand across tumor types. This growth is broad-based from both continued expansion of newer indications such as ADRIATIC and small-cell lung cancer, and NIAGARA and bladder cancer, as well as increased uptake of more established indications such as HIMALAYA and liver cancer. Calquence total revenues increased 17% in the fourth quarter, driven by additional demand in front-line CLL as we maintain our class leadership position across major markets.
Speaker #2: With all our medicines key regions revenues in demonstrating double digit growth . Tagrisso global were revenues reflecting continued up 10% , demand growth across all indications in the first line setting .
Speaker #2: We are now seeing a significant proportion of receiving a patients combination regimen , with Flaura two being the clear preference across key markets in earlier increased adoption of Adaura and been another meaningful source of growth in and Imjudo , 37 and 26% growth , respectively , reflecting Laura has continued demand across tumor types .
Speaker #2: growth is based from both continued newer broad indications such as delivered Finzi and small cell lung cancer , Niagara in and bladder cancer , as This well as increased uptake of more established expansion of indications such as Himalaya and cancer liver .
Speaker #2: increased 17% in the revenues fourth quarter , driven by demand Calquence total additional in frontline CLL . As maintain we our leadership class position Adriatic across major markets , specifically in the United States , we've market share , leadership course of seen our year over the , demonstrating our grow competitive positioning and differentiation in Her2 delivered total revenue growth of 46% in the fourth quarter across all regions in is seeing share gains both Her2 positive Her2 low and breast metastatic and in China , cancer demand continues to increase following Nrdl the enlistment in January of last year , Truqap 41% in the revenues grew fourth year over year quarter , with benefiting from both inventory build in comparisons the US of reversal pricing In Europe .
Dave Fredrickson: Specifically, in the United States, we've seen our market share leadership grow over the course of the year, demonstrating our competitive positioning and differentiation. Enhertu delivered total revenue growth of 46% in Q4. Across all regions, Enhertu is seeing share gains both in HER2-positive and HER2-low metastatic breast cancer. In China, demand continues to increase following NRDL enlistment in January of last year. Truqap revenues grew 41% in Q4, with year-over-year comparisons benefiting from both inventory build in the US and the reversal of pricing accruals in Europe. In the US, we now believe Truqap is at peak, with further incremental growth to be driven by other markets. Finally, Dato-DXd revenues of $40 million in Q4 reflect our early launch momentum in late-line EGFR-mutated lung cancer, including an emerging leadership position in the third-line. Next slide, please.
Dave Fredrickson: Specifically, in the United States, we've seen our market share leadership grow over the course of the year, demonstrating our competitive positioning and differentiation. Enhertu delivered total revenue growth of 46% in Q4. Across all regions, Enhertu is seeing share gains both in HER2-positive and HER2-low metastatic breast cancer. In China, demand continues to increase following NRDL enlistment in January of last year. Truqap revenues grew 41% in Q4, with year-over-year comparisons benefiting from both inventory build in the US and the reversal of pricing accruals in Europe. In the US, we now believe Truqap is at peak, with further incremental growth to be driven by other markets. Finally, Dato-DXd revenues of $40 million in Q4 reflect our early launch momentum in late-line EGFR-mutated lung cancer, including an emerging leadership position in the third-line. Next slide, please.
Dave Fredrickson: The strong momentum in 2025 continues into 2026. For Imfinzi, we were pleased to see the US approval for Matterhorn and early gastric cancer at the end of November, and are already seeing encouraging uptake. Potomac and bladder cancer will add another growth opportunity this year, with the first approval expected in the first half. We expect data in 2026 for several Imfinzi combinations, including Imjudo, bladder cancer, and HCC, and with Dato-DXd and lung, with commercial launches planned in 2027 pending, of course, positive results and regulatory approvals. 2026 is set to be another landmark year for Enhertu as we further expand our position as the standard of care in HER2-positive breast cancer by bringing this transformational medicine to three new settings.
Dave Fredrickson: The strong momentum in 2025 continues into 2026. For Imfinzi, we were pleased to see the US approval for Matterhorn and early gastric cancer at the end of November, and are already seeing encouraging uptake. Potomac and bladder cancer will add another growth opportunity this year, with the first approval expected in the first half. We expect data in 2026 for several Imfinzi combinations, including Imjudo, bladder cancer, and HCC, and with Dato-DXd and lung, with commercial launches planned in 2027 pending, of course, positive results and regulatory approvals. 2026 is set to be another landmark year for Enhertu as we further expand our position as the standard of care in HER2-positive breast cancer by bringing this transformational medicine to three new settings.
Speaker #2: Next slide, please. The strong momentum in 2025 into 2026 for infancy. We were pleased to see the US Matterhorn for gastric in early cancer at the end of November, already encouraging continued uptake.
Speaker #2: Potomac and bladder cancer will add another growth opportunity this year , with the first approval expected in , and are first half . We expect data in 2026 for several infancy combinations , including imjudo and bladder cancer , and with Detroit HCC , and Lung with commercial launches planned course , positive .
Speaker #2: Results and regulatory approvals—be it in another, 2026 is set to be a landmark year for us. Enhertu, we will further expand as the standard of care in the positive breast setting in 2027 by bringing this transformational HER2 medicine to three new settings.
Dave Fredrickson: This includes the first-line metastatic setting following the recent approval of DESTINY-Breast09, with approvals in early breast cancer for DESTINY-Breast11 and DESTINY-Breast05 also expected this year. Looking to 2027 and beyond, we remain focused on bringing Enhertu to more patients globally, including in settings beyond breast cancer such as lung cancer. For Calquence, we expect the imminent US launch of the Amplify fixed-duration therapy regimen to be an important driver of growth for the year. This complements the sustained demand in the treat-to-progression segment within first-line CLL, where Calquence remains the leading BTK inhibitor. Looking ahead, we aim to leverage our broader hematology portfolio to improve outcomes through combination approaches in CLL as well as in other hematologic malignancies.
Dave Fredrickson: This includes the first-line metastatic setting following the recent approval of DESTINY-Breast09, with approvals in early breast cancer for DESTINY-Breast11 and DESTINY-Breast05 also expected this year. Looking to 2027 and beyond, we remain focused on bringing Enhertu to more patients globally, including in settings beyond breast cancer such as lung cancer. For Calquence, we expect the imminent US launch of the Amplify fixed-duration therapy regimen to be an important driver of growth for the year. This complements the sustained demand in the treat-to-progression segment within first-line CLL, where Calquence remains the leading BTK inhibitor. Looking ahead, we aim to leverage our broader hematology portfolio to improve outcomes through combination approaches in CLL as well as in other hematologic malignancies.
Speaker #2: includes the This first line metastatic the setting . Following approval of , with Destiny-breast01 approvals in breast early for Destiny-breast01 and Db05 . Also expected cancer this , looking to beyond , 2027 and we remain focused on bringing Enhertu to more patients globally , including in settings breast cancer such as lung cancer .
Speaker #2: For Calquence, we expect the imminent US launch of the Amplify-Year Finite Therapy regimen to be an important driver of growth for the year.
Speaker #2: This complements the sustained demand in the progression treat to within first-line HCL, where Calquence remains leading the BTK segment inhibitor looking.
Speaker #2: Ahead, we aim to leverage our portfolio to improve hematology outcomes through combination approaches. In CLL, as well as more broadly in other hematologic malignancies.
Dave Fredrickson: Building on double-digit growth for Tagrisso in 2025, we anticipate strong performance in 2026, driven by further adoption and geographic expansion of LAURA and ADAURA in early disease, and sustained leadership in first-line metastatic disease, particularly within the growing combination market. Longer term, we look forward to the results of multiple combination trials that have the potential to reinforce Tagrisso as the backbone TKI, both in later lines with Savolitinib and TROPION-Lung15, and in the front line with TROPION-Lung14. As we reflect on another strong year of growth, we continue to see sustained momentum in our oncology business heading into 2026, with a clear focus on expanding the reach of our medicines into new markets and with additional indications. With that, please advance to the next slide. I'll hand over to Susan, who will discuss our key readouts that we anticipate this year.
Dave Fredrickson: Building on double-digit growth for Tagrisso in 2025, we anticipate strong performance in 2026, driven by further adoption and geographic expansion of LAURA and ADAURA in early disease, and sustained leadership in first-line metastatic disease, particularly within the growing combination market. Longer term, we look forward to the results of multiple combination trials that have the potential to reinforce Tagrisso as the backbone TKI, both in later lines with Savolitinib and TROPION-Lung15, and in the front line with TROPION-Lung14. As we reflect on another strong year of growth, we continue to see sustained momentum in our oncology business heading into 2026, with a clear focus on expanding the reach of our medicines into new markets and with additional indications. With that, please advance to the next slide. I'll hand over to Susan, who will discuss our key readouts that we anticipate this year.
Speaker #2: Building on double-digit growth, Tagrisso was strong in 2025. We anticipate performance driven by further adoption in geographic expansion in 2026, Laura, and expansion of early disease and sustained leadership in first line, particularly within the Adora and growing metastatic combination market.
Speaker #2: Longer term , we look forward to the of multiple results trials that have the potential to reinforce Tagrisso as the TKI , lines with backbone saffron and later lung in front line 15 and in the with As we reflect on another strong year of growth , we continue to see sustained momentum in our oncology business heading into 2026 with a clear focus expanding the on reach of our medicines into new combination markets and with additional indications .
Speaker #2: With that , please advance to the next slide . I'll hand over to Susan , who will lung 14 . discuss our key readouts that we anticipate year this both .
Susan Galbraith: Thank you, Dave. Momentum continues to build across our oncology portfolio. As we enter 2026 with a robust pipeline, we have an important opportunity to advance therapies for patients with high unmet needs. Today, I want to spotlight several key catalysts supporting our continued growth, starting with our TROP2 ADC, Dato-DXd. Last year, we saw Dato-DXd demonstrate its profile as best-in-class TROP2 ADC, with launches in HR-positive breast cancer and later-line EGFR-mutated lung cancer, and with compelling data presented at ESMO in triple-negative breast cancer, demonstrating a five-month improvement in overall survival versus standard-of-care chemotherapy. TROPION-Breast02 has now been accepted by the FDA for priority review. This year, we expect the readout for AVANZAR, a pivotal trial evaluating Dato-DXd as the first-line lung cancer setting. AVANZAR investigates the combination of Dato-DXd with Imfinzi and carboplatin, aiming to deepen and extend responses for this large, high-unmet-need population.
Susan Galbraith: Thank you, Dave. Momentum continues to build across our oncology portfolio. As we enter 2026 with a robust pipeline, we have an important opportunity to advance therapies for patients with high unmet needs. Today, I want to spotlight several key catalysts supporting our continued growth, starting with our TROP2 ADC, Dato-DXd. Last year, we saw Dato-DXd demonstrate its profile as best-in-class TROP2 ADC, with launches in HR-positive breast cancer and later-line EGFR-mutated lung cancer, and with compelling data presented at ESMO in triple-negative breast cancer, demonstrating a five-month improvement in overall survival versus standard-of-care chemotherapy. TROPION-Breast02 has now been accepted by the FDA for priority review. This year, we expect the readout for AVANZAR, a pivotal trial evaluating Dato-DXd as the first-line lung cancer setting. AVANZAR investigates the combination of Dato-DXd with Imfinzi and carboplatin, aiming to deepen and extend responses for this large, high-unmet-need population.
Speaker #3: Thank you . Dave . continues to build momentum across our oncology portfolio . And as we enter robust 2026 with a pipeline , an important advance opportunity to therapies for patients with high needs .
Speaker #3: Today , I unmet want to spotlight several key catalysts supporting our continued growth . Starting with our ADC Trop2 Dashaway . Last year , we saw data demonstrate its profile as best in class Trop2 , we have ADC with launches HR , positive in Breast cancer and later mutated lung cancer and with data presented ESMO in triple at negative breast cancer , demonstrating a five month improvement in survival versus standard of care chemotherapy EGFR .
Speaker #3: Tropium Bristow compelling two has now been accepted by the FDA for priority review . This year , expect the we Avanza , readout for a pivotal trial evaluating Dashaway as the first line lung cancer setting Avanza investigates the combination of data with FMC and aiming carboplatin , deepen and to responses for this high large , unmet need .
Susan Galbraith: Crucially, AVANZAR will be the first trial to validate our QCS TROP2 NME biomarker, designed to identify patients most likely to respond to Dato-DXd in this first-line lung cancer setting. Success here could enable broader application of this technology in other tumor types and across our ADC portfolio. Building on Dato-DXd's current approval in later-line EGFR-mutated lung cancer, we also anticipate the readout from TROPION-Lung15, which evaluates Dato-DXd alone or in combination with Tagrisso for patients who have progressed on a TKI. This trial aims to set new standards for second-line treatment, further reinforcing Tagrisso's role as the backbone of care in EGFR-mutant lung cancer and paving the way for TROPION-Lung14 in first-line setting, which can build on the success of FLAURA and FLAURA2. Imfinzi continues to deliver transformative benefits across cancer types.
Susan Galbraith: Crucially, AVANZAR will be the first trial to validate our QCS TROP2 NME biomarker, designed to identify patients most likely to respond to Dato-DXd in this first-line lung cancer setting. Success here could enable broader application of this technology in other tumor types and across our ADC portfolio. Building on Dato-DXd's current approval in later-line EGFR-mutated lung cancer, we also anticipate the readout from TROPION-Lung15, which evaluates Dato-DXd alone or in combination with Tagrisso for patients who have progressed on a TKI. This trial aims to set new standards for second-line treatment, further reinforcing Tagrisso's role as the backbone of care in EGFR-mutant lung cancer and paving the way for TROPION-Lung14 in first-line setting, which can build on the success of FLAURA and FLAURA2. Imfinzi continues to deliver transformative benefits across cancer types.
Speaker #3: Population. Crucially, Avanza will be the first trial to validate our QRx Trop2 NMR biomarker, designed to identify patients most likely to respond to data in the lung cancer setting. In this first line, success.
Speaker #3: Here could enable broader application of this technology in other tumor types and across our ADC portfolio . Building Dutch Airway's on current approval in later EGFR mutated lung cancer , we also anticipate the readout from Tropine Lung 15 , which evaluates D4 alone or in combination with patients who Tagrisso for have progressed on a TKI trial , this aims to set new for second line standards treatment .
Speaker #3: Further reinforcing Tigresses backbone of care in EGFR role as the mutant lung cancer and paving the way for Tropine lung in first line 14 setting , build on the which can success of flora and flora two .
Susan Galbraith: This year's key readouts in GI, lung, and bladder cancer signal a third wave of Imfinzi growth, highlighting the potential of combination regimens. I want to highlight two today. Firstly, the EMERALD3 trial aims to bring the combination of Imfinzi and Imjudo into the local regional setting for hepatocellular carcinoma, building on the transformative results we've already demonstrated in the later-line HIMALAYA trial. Secondly, VOLGA looks to build on our existing presence in muscle-invasive bladder cancer. The NIAGARA regimen established a role for Imfinzi as the first perioperative immunotherapy regimen in cisplatin-eligible patients. VOLGA explores whether the combination of enfortumab vedotin and Imfinzi, plus or minus Imjudo, can improve outcomes for the 50% of patients that are not candidates for cisplatin. This regimen is differentiated in two important ways. First, enfortumab vedotin is limited to the neoadjuvant setting, aiming to optimize outcomes while balancing the overall benefit-risk profile.
Susan Galbraith: This year's key readouts in GI, lung, and bladder cancer signal a third wave of Imfinzi growth, highlighting the potential of combination regimens. I want to highlight two today. Firstly, the EMERALD3 trial aims to bring the combination of Imfinzi and Imjudo into the local regional setting for hepatocellular carcinoma, building on the transformative results we've already demonstrated in the later-line HIMALAYA trial. Secondly, VOLGA looks to build on our existing presence in muscle-invasive bladder cancer. The NIAGARA regimen established a role for Imfinzi as the first perioperative immunotherapy regimen in cisplatin-eligible patients. VOLGA explores whether the combination of enfortumab vedotin and Imfinzi, plus or minus Imjudo, can improve outcomes for the 50% of patients that are not candidates for cisplatin. This regimen is differentiated in two important ways. First, enfortumab vedotin is limited to the neoadjuvant setting, aiming to optimize outcomes while balancing the overall benefit-risk profile.
Speaker #3: In FMC, transformative continues to deliver benefits across types of cancer. Key this year's in GI and bladder cancers, readouts signal a third wave of lung, and potential of combination regimens.
Speaker #3: I want to highlight two today. Firstly, the Emerald-3 trial aims to bring the combination of Imfinzi and Imjudo into the local regional setting for hepatocellular carcinoma.
Speaker #3: Building on the transformative results we've demonstrated already in the later line , trial Himalaya . Secondly , to build on our existing Volga looks presence in muscle invasive bladder cancer .
Speaker #3: established a role for Imfinzi as first perioperative the regimen in The immunotherapy cisplatin cisplatin , eligible patients , Volga explores whether the combination of enforcement of vedotin and imfinzi plus or minus imjudo can improve outcomes for the 50% of patients that are not candidates for regimen cisplatin .
Speaker #3: is differentiated in ways two important . First , This of the enforcement dosing is limited to the neoadjuvant setting . Aiming to balancing the outcomes while overall optimize profile acknowledging secondly , cancers bladder sensitivity to Ctla four blockade Volga includes an delivering three cycles of arm , two Pre-operatively and Post-operatively , with the goal of further Imjudo one patient responses deepening population in this .
Susan Galbraith: And secondly, acknowledging bladder cancer's sensitivity to CTLA4 blockade, VOLGA includes an arm delivering three cycles of Imjudo, two preoperatively and one postoperatively, with the goal of further deepening responses in this patient population. In 2026, we will also see the second pivotal readout for Camizestrant, our next-generation oral SERD. Last year, we shared the first phase III data for Camizestrant in patients with first-line hormone receptor-positive disease with emerging ESR1 mutations. The transformational SARINA6 results demonstrated that intervening at the earliest opportunity and switching to a more effective endocrine option ahead of progression with Camizestrant and switching with Camizestrant offers the chance to retain control of a patient's disease for longer and thereby realizes the full potential of first-line treatment.
Susan Galbraith: And secondly, acknowledging bladder cancer's sensitivity to CTLA4 blockade, VOLGA includes an arm delivering three cycles of Imjudo, two preoperatively and one postoperatively, with the goal of further deepening responses in this patient population. In 2026, we will also see the second pivotal readout for Camizestrant, our next-generation oral SERD. Last year, we shared the first phase III data for Camizestrant in patients with first-line hormone receptor-positive disease with emerging ESR1 mutations. The transformational SARINA6 results demonstrated that intervening at the earliest opportunity and switching to a more effective endocrine option ahead of progression with Camizestrant and switching with Camizestrant offers the chance to retain control of a patient's disease for longer and thereby realizes the full potential of first-line treatment.
Speaker #3: In will also see the 2026 . readout for We Camizestrant on next oral generation serd year , we shared the . Last patients Camizestrant in with hormone data for positive disease , first line with first phase three emerging ESL the transformational Serena demonstrated that intervening at receptor earliest one mutations , six results opportunity to a endocrine switching option ahead more effective progression with Camizestrant ahead of of progression switching with Camizestrant offers the chance to retain control and of a patient's and longer disease full realizes the potential of first line treatment .
Susan Galbraith: In the second half of this year, SERENA4 will readout, targeting a broader, upfront first-line population eligible for the combination of a CDK4/6 inhibitor and an aromatase inhibitor, and assessing whether Camizestrant can replace the aromatase inhibitor to improve outcomes. Our confidence is driven not only by our data from the phase II SERENA2 and the phase III SERENA6 results, but also from recent readouts in the competitive space that demonstrate the value of this class in ESR1 wild-type, endocrine-sensitive disease. Finally, progress is accelerating across our ADC portfolio, with AZD0901, our claudin 18.2 targeted ADC, on track to deliver its first phase III data in second-line gastric cancer in the first half of the year. These six trials represent only a fraction of the opportunities of our oncology portfolio, which is poised to drive continued growth.
Susan Galbraith: In the second half of this year, SERENA4 will readout, targeting a broader, upfront first-line population eligible for the combination of a CDK4/6 inhibitor and an aromatase inhibitor, and assessing whether Camizestrant can replace the aromatase inhibitor to improve outcomes. Our confidence is driven not only by our data from the phase II SERENA2 and the phase III SERENA6 results, but also from recent readouts in the competitive space that demonstrate the value of this class in ESR1 wild-type, endocrine-sensitive disease. Finally, progress is accelerating across our ADC portfolio, with AZD0901, our claudin 18.2 targeted ADC, on track to deliver its first phase III data in second-line gastric cancer in the first half of the year. These six trials represent only a fraction of the opportunities of our oncology portfolio, which is poised to drive continued growth.
Speaker #3: In the second half of this year , Serena four will read out broader targeting a upfront first line population eligible for the combination of a Cdk4 six inhibitor and an aromatase and inhibitor , assessing whether Camizestrant can replace the aromatase inhibitor to improve outcomes .
Speaker #3: confidence is driven not Our only data by our from the phase two Serena two and phase three Serena six results , but also from recent readouts in the competitive space that demonstrate the value of this class in Esr1 wild endocrine sensitive disease progress is accelerating type across our ADC portfolio with sunny V , our Claudin 18.2 targeted ADC track on to deliver its first phase three data gastric cancer .
Speaker #3: In the first half of the year . These six trials represent only a fraction of the opportunities of our oncology portfolio , which is poised to drive continued growth and throughout the year , we'll continue to updates from our early pipeline , reinforcing confidence in our progress on our transformative technologies , and therefore long term growth .
Susan Galbraith: Throughout the year, we'll continue to share updates from our early pipeline, reinforcing confidence in progress on our transformative technologies and therefore long-term growth prospects through 2030 and beyond. With that, please advance to the next slide, and I'll pass over to Ruud to cover BioPharmaceuticals performance.
Susan Galbraith: Throughout the year, we'll continue to share updates from our early pipeline, reinforcing confidence in progress on our transformative technologies and therefore long-term growth prospects through 2030 and beyond. With that, please advance to the next slide, and I'll pass over to Ruud to cover BioPharmaceuticals performance.
Speaker #3: Through 2030 and beyond with. And with that, advance to the next slide, please, and I'll pass over to Ruud to cover biopharmaceuticals performance prospects.
Ruud Dobber: Thank you very much, Susan. Next slide, please. Our biopharmaceuticals medicines delivered strong performance in 2025, with total revenue up 5% to $23 billion, with our growth medicines substantially outpacing the impact of generic entry on a limited number of brands, such as Brilinta in the US and Europe, and Farxiga in the UK. In Q4, RNI revenues were up by 10%, with revenue from growth medicines having increased by 27%. CVRM revenues were 6% down on the prior year, with generic competition slowing Farxiga's growth to 2% and Brilinta continuing to decline. VNI total revenue was down 33% year-over-year, largely due to the Beyfortus sales milestone booked in Q4 2024. Next slide, please. Biologic medicines continue to gain share among severe asthma patients.
Ruud Dobber: Thank you very much, Susan. Next slide, please. Our biopharmaceuticals medicines delivered strong performance in 2025, with total revenue up 5% to $23 billion, with our growth medicines substantially outpacing the impact of generic entry on a limited number of brands, such as Brilinta in the US and Europe, and Farxiga in the UK. In Q4, RNI revenues were up by 10%, with revenue from growth medicines having increased by 27%. CVRM revenues were 6% down on the prior year, with generic competition slowing Farxiga's growth to 2% and Brilinta continuing to decline. VNI total revenue was down 33% year-over-year, largely due to the Beyfortus sales milestone booked in Q4 2024. Next slide, please. Biologic medicines continue to gain share among severe asthma patients.
Speaker #3: to
Speaker #4: Thank you very much, Susan. Next slide, please. Our biopharmaceuticals medicines delivered strong performance in revenue in 2025, with total up 5% to $23 billion.
Speaker #4: Gross medicines substantially—the impact of generic entry is limited, outpacing brands' numbers, with our, as in the United States and Brilinta, and the Europe.
Speaker #4: And Forxiga in the United Kingdom on a . In the fourth quarter , RNAi revenues were up by 10% , with revenue from growth medicines having increased by 27% , CRM revenues were 6% down on the prior year , with generic competition slowing for Sega's growth to 2% and Brilinta continuing to decline was revenue .
Speaker #4: Fini down 33% year on year, 40 sales Bay largely due to the milestone booked in the fourth quarter of 2024. Please, next slide.
Ruud Dobber: Our medicines now make up more than half of the new-to-brand prescriptions for the severe asthma biologic segment in several markets. Fasenra is the leading IL-5 medicine for severe eosinophilic asthma, and its product profile was recently strengthened with the launch of the EGPA indication. Overall, we expect Fasenra's positive momentum to continue in 2026, with growth in the emerging markets set to accelerate following inclusion in the National Reimbursement Drug List in China. Tezspire has made rapid market share gains in severe asthma since its launch, and its growth potential has been enhanced by recent approvals for use in chronic rhinosinusitis with nasal polyps, where Tezspire has demonstrated that it can nearly eliminate the need for surgery. Nasal polyps are a common comorbidity for asthma patients, so this approval further enhances its clinical profile. Breztri is the fastest-growing medicine within the expanding COPD.
Ruud Dobber: Our medicines now make up more than half of the new-to-brand prescriptions for the severe asthma biologic segment in several markets. Fasenra is the leading IL-5 medicine for severe eosinophilic asthma, and its product profile was recently strengthened with the launch of the EGPA indication. Overall, we expect Fasenra's positive momentum to continue in 2026, with growth in the emerging markets set to accelerate following inclusion in the National Reimbursement Drug List in China. Tezspire has made rapid market share gains in severe asthma since its launch, and its growth potential has been enhanced by recent approvals for use in chronic rhinosinusitis with nasal polyps, where Tezspire has demonstrated that it can nearly eliminate the need for surgery. Nasal polyps are a common comorbidity for asthma patients, so this approval further enhances its clinical profile. Breztri is the fastest-growing medicine within the expanding COPD.
Speaker #4: Biologic medicines continue to gain among severe asthma patients. Our share medicines now make up more than half of the new brand prescriptions for the asthma biologic segment in several markets.
Speaker #4: Fasenra is the leading medicine in IL-5 for severe eosinophilic asthma. Its product profile was recently strengthened with the launch in EGPA.
Speaker #4: We expect indication for Sandra's positive overall. We expect momentum to continue into 2026, with growth in emerging markets set to accelerate following inclusion in the national drug reimbursement list in China. This has helped us gain market share.
Speaker #4: in gains asthma rapid Despite launch , and since its its growth potential has been recent use in approvals for chronic nasal , where has with Tezspire it can nearly demonstrated that enhanced by the need surgery .
Speaker #4: Are nasal polyps a common comorbidity for patients with asthma? So, this elimination enhances its clinical profile. Approval for Breztri as the fastest-growing medicine for nasal polyps is important.
Ruud Dobber: We are the clear market leader in China and have been gaining share in most other major markets. Additionally, regulatory reviews are underway for asthma based on the KALOS and LOGOS trials, and we anticipate first approvals in the first half of 2026. Saphnelo, our biological medicine for the treatment of SLE, is continuing to grow strongly, with the IV formulation having gained market leadership in several major markets. Saphnelo's subcutaneous formulation was recently approved in Europe and will extend its reach to the larger segment of patients who favor self-administration. We are expecting further approvals of subcutaneous Saphnelo in other regions this year, including in the United States and Japan in the first half. 2026 marks a transition year for our CVRM franchise. We anticipate Lokelma's strong growth to continue into 2026, driven by market leadership within the growing potassium binder class.
Ruud Dobber: We are the clear market leader in China and have been gaining share in most other major markets. Additionally, regulatory reviews are underway for asthma based on the KALOS and LOGOS trials, and we anticipate first approvals in the first half of 2026. Saphnelo, our biological medicine for the treatment of SLE, is continuing to grow strongly, with the IV formulation having gained market leadership in several major markets. Saphnelo's subcutaneous formulation was recently approved in Europe and will extend its reach to the larger segment of patients who favor self-administration. We are expecting further approvals of subcutaneous Saphnelo in other regions this year, including in the United States and Japan in the first half. 2026 marks a transition year for our CVRM franchise. We anticipate Lokelma's strong growth to continue into 2026, driven by market leadership within the growing potassium binder class.
Speaker #4: within The expanding OPD , we are the market leader clear in China have been gaining share in most other major markets . Additionally , regulatory reviews are underway for asthma based on the Kalos and Locus trials , and we approvals in and the first half anticipate further of 2026 .
Speaker #4: Saphnelo, a biological medicine for SLE, is for the continuing treatment of strongly, with the IV formulation having to grow. Market gained leadership in several major markets. Saphnelo subcutaneous recently, formulation was approved in Europe and will extend the reach to its segment largest of patients who favor or are expecting self-administration further.
Speaker #4: Approvals of We subcutaneous sulfonilo regions, other this in including in the United States and Japan. In the first half, 2026 marks the transition year for our CRM franchise. We anticipate local growth too.
Ruud Dobber: We have also increased additional manufacturing capacity to support our growth ambitions. In 2026, as mentioned, we anticipate Farxiga VBP implementation in China during Q1 and the first generic competition in the United States in April. While Farxiga revenues in the United States, Japan, and China are expected to decline this year, we anticipate strong demand growth to continue in Europe and the emerging markets. Looking beyond 2026, dapagliflozin fixed-dose combinations have the potential to unlock new waves of medicines for patients, and we already have three fixed-dose combinations of dapagliflozin in phase III development, with the first two phase III trials due to readout in 2027. We are currently preparing for the launch of Baxdrostat in uncontrolled and treatment-resistant hypertension. The U.S. approval is anticipated to broadly coincide with the entry of generic dapagliflozin in this market, allowing us to leverage our existing commercial infrastructure.
Ruud Dobber: We have also increased additional manufacturing capacity to support our growth ambitions. In 2026, as mentioned, we anticipate Farxiga VBP implementation in China during Q1 and the first generic competition in the United States in April. While Farxiga revenues in the United States, Japan, and China are expected to decline this year, we anticipate strong demand growth to continue in Europe and the emerging markets. Looking beyond 2026, dapagliflozin fixed-dose combinations have the potential to unlock new waves of medicines for patients, and we already have three fixed-dose combinations of dapagliflozin in phase III development, with the first two phase III trials due to readout in 2027. We are currently preparing for the launch of Baxdrostat in uncontrolled and treatment-resistant hypertension. The U.S. approval is anticipated to broadly coincide with the entry of generic dapagliflozin in this market, allowing us to leverage our existing commercial infrastructure.
Speaker #4: continue into 2026, driven by market leadership within the growing binder potassium class. We have increased additional manufacturing capacity to support our growth ambitions.
Speaker #4: In 2026, as mentioned, we anticipate Farxiga EVP implementation in China during the first quarter, first generic, and the competition in the United States in April.
Speaker #4: While Farxiga revenues in the United States, Japan, and China are expected to decline this year, we anticipate strong demand and growth to continue in Europe and the emerging markets.
Speaker #4: Beyond looking to 2026, the combinations have dapagliflozin fixed dose potential to unlock new waves of medicines for patients. We already have three fixed dose combinations with dapagliflozin in Phase 3 development, with the first of the Phase 3 trials due to read out in 2027.
Speaker #4: We are currently preparing for the Dextrostat in launch of uncontrolled and treatment resistant The US hypertension . approval is anticipated to broadly coincide with the entry of generic dapagliflozin in this market , allowing us to leverage our existing commercial infrastructure .
Ruud Dobber: While Baxdrostat will not be a major contributor to revenues in 2026, the clinical data supporting its use is compelling, and the long-term potential of this medicine is substantial, with peak revenues from the product from this product franchise expected to exceed $5 billion. I will now hand over to Sharon, who will provide further details on the upcoming developments in our pipeline, including Wainua and ATTR cardiomyopathy, which represents a major potential growth driver for the biopharmaceuticals business.
Ruud Dobber: While Baxdrostat will not be a major contributor to revenues in 2026, the clinical data supporting its use is compelling, and the long-term potential of this medicine is substantial, with peak revenues from the product from this product franchise expected to exceed $5 billion. I will now hand over to Sharon, who will provide further details on the upcoming developments in our pipeline, including Wainua and ATTR cardiomyopathy, which represents a major potential growth driver for the biopharmaceuticals business.
Speaker #4: While Baxter will not be a major contributor to revenues in 2026, clinical data supporting its use is compelling, and the long-term potential of this medicine is substantial.
Speaker #4: With peak revenues product , from from this product from the franchise expected to exceed $5 billion . I will now hand over to Sharon , who provide will further details on the developments upcoming in our pipeline Wainua and , including cardiomyopathy , which represents Attr major driver for the biopharmaceuticals business .
Sharon Barr: Thanks, VUD. Next slide, please. We saw strong progress across our biopharma clinical pipeline in 2025 and are entering 2026 with a broad and deep pipeline across CVRM and R&I. Today, I want to highlight two high-value phase III catalysts anticipated this year, positioned to deliver meaningful impact for patients and AstraZeneca's growth ambition. Starting with Wainua, we expect the CardioTransform readout in ATTR-CM in the second half of this year. Wainua is an antisense oligonucleotide designed selectively to suppress hepatic production of transthyretin, addressing the upstream driver of amyloid fibril formation. ATTR-CM is often underdiagnosed as symptoms overlap with common cardiac issues, leading to delayed diagnosis, poor prognosis, and high morbidity. This highlights the need for better diagnostics and innovative new treatment options.
Sharon Barr: Thanks, VUD. Next slide, please. We saw strong progress across our biopharma clinical pipeline in 2025 and are entering 2026 with a broad and deep pipeline across CVRM and R&I. Today, I want to highlight two high-value phase III catalysts anticipated this year, positioned to deliver meaningful impact for patients and AstraZeneca's growth ambition. Starting with Wainua, we expect the CardioTransform readout in ATTR-CM in the second half of this year. Wainua is an antisense oligonucleotide designed selectively to suppress hepatic production of transthyretin, addressing the upstream driver of amyloid fibril formation. ATTR-CM is often underdiagnosed as symptoms overlap with common cardiac issues, leading to delayed diagnosis, poor prognosis, and high morbidity. This highlights the need for better diagnostics and innovative new treatment options.
Speaker #5: Thanks, Ruud. Next slide, please. We saw strong progress across our biopharma clinical pipeline in 2025 and are entering 2026 with a broad and deep pipeline across CVM and.
Speaker #5: RNAi I want Today , to highlight two high value three catalysts phase this anticipated year , positioned to deliver meaningful impact for patients and AstraZeneca growth ambition , starting with Wainua , we expect the cardio transform readout in in the cardiomyopathy Attr second half of this year .
Speaker #5: Wainua is an antisense oligonucleotide designed selectively to suppress hepatic production of transthyretin, addressing the upstream driver of amyloid fibril formation. ATTR cardiomyopathy often has overlap with common symptoms in cardiac disease, leading to delayed diagnosis.
Speaker #5: Poor delayed high morbidity issues prognosis , and . This highlights the for better need innovative diagnostics and new treatment options . Cardio transform largest the is study ever conducted in this disease enrolling more than 1400 patients to , receive wainua or placebo on top of standard of care for 140 weeks .
Sharon Barr: CardioTransform is the largest study ever conducted in this disease, enrolling more than 1,400 patients to receive Wainua or placebo on top of standard of care for 140 weeks. The trial's primary endpoint is a robust composite of cardiovascular mortality and recurrent cardiovascular clinical events designed to capture clinically meaningful outcomes. Importantly, Wainua can be administered once monthly as a single dose via a subcutaneous autoinjector, enabling convenient at-home dosing. That's an advantage for this largely aging population. Wainua represents just one component of our leading amyloidosis portfolio. We believe that multiple mechanisms of action will be needed to address the full spectrum of ATTR cardiomyopathy, and we look forward to initiating clinical development of Wainua in combination with our depletor, Coramitug, in the near future.
Sharon Barr: CardioTransform is the largest study ever conducted in this disease, enrolling more than 1,400 patients to receive Wainua or placebo on top of standard of care for 140 weeks. The trial's primary endpoint is a robust composite of cardiovascular mortality and recurrent cardiovascular clinical events designed to capture clinically meaningful outcomes. Importantly, Wainua can be administered once monthly as a single dose via a subcutaneous autoinjector, enabling convenient at-home dosing. That's an advantage for this largely aging population. Wainua represents just one component of our leading amyloidosis portfolio. We believe that multiple mechanisms of action will be needed to address the full spectrum of ATTR cardiomyopathy, and we look forward to initiating clinical development of Wainua in combination with our depletor, Coramitug, in the near future.
Speaker #5: The trial's primary endpoint is a robust composite of cardiovascular recurrent mortality and cardiovascular clinical events, designed to capture clinically meaningful outcomes. Importantly, Wainua can be administered once monthly as a single dose via subcutaneous injection, enabling convenient at-home dosing.
Speaker #5: That's an advantage for an autoinjector, largely due to the aging population. Wainua represents just one component of our amyloidosis portfolio. We believe that leading multiple mechanisms of action will be needed to address the full spectrum of ATTR cardiomyopathy, and we look forward to initiating clinical development of Wainua in combination with a depleter in the near future.
Sharon Barr: Turning now to the phase III program for our differentiated IL-33 biologic, tozorakimab in COPD, which we anticipate will readout in the first half of this year. We have three trials ongoing: Oberon, Titania, and Miranda, which have the potential to redefine the management of this complex, heterogeneous, and progressive disease. The trials all have the same primary endpoint: the reduction in annualized rate of moderate to severe COPD exacerbations in former smokers. The program will also evaluate efficacy in a broader COPD population, irrespective of eosinophil count or smoking status, and explores a range of dosing regimens to maximize the potential population that could benefit from tozorakimab. Should the results be positive, tozorakimab could be the first-in-class IL-33 biologic for COPD. I also wanted to take the opportunity to highlight advances in our weight management portfolio.
Sharon Barr: Turning now to the phase III program for our differentiated IL-33 biologic, tozorakimab in COPD, which we anticipate will readout in the first half of this year. We have three trials ongoing: Oberon, Titania, and Miranda, which have the potential to redefine the management of this complex, heterogeneous, and progressive disease. The trials all have the same primary endpoint: the reduction in annualized rate of moderate to severe COPD exacerbations in former smokers. The program will also evaluate efficacy in a broader COPD population, irrespective of eosinophil count or smoking status, and explores a range of dosing regimens to maximize the potential population that could benefit from tozorakimab. Should the results be positive, tozorakimab could be the first-in-class IL-33 biologic for COPD. I also wanted to take the opportunity to highlight advances in our weight management portfolio.
Speaker #5: Turning now to the Phase 3 program for our differentiated IL-33 biologic in which we, COPD, anticipate will read out in the first half of this year.
Speaker #5: We have three trials ongoing . Oberon , Titania and Miranda , which have the redefine the management of potential to complex , heterogeneous and progressive disease .
Speaker #5: The trials all have the same primary endpoint the reduction in annualized rate of moderate to severe COPD exacerbations in former smokers . The will program also evaluate efficacy in a broader COPD population , irrespective of eosinophil count or smoking status , and explores a range of maximize regimens to the potential population that .
Speaker #5: Should the from could tocilizumab results be positive , tuzumab could be the first in 33 class IL biologic for COPD . I also wanted to take the opportunity to highlight advances in our weight management portfolio .
Sharon Barr: We are delighted to announce today that our once-daily oral GLP-1 receptor agonist, Ecoglipron, formerly known as AZD5004, met its primary endpoints in both the VISTA and SOLSTICE phase IIb trials conducted in people with obesity or type 2 diabetes, respectively. We look forward to sharing these data at the American Diabetes Association meeting in June. Based on the strength of these data, we are progressing Ecoglipron into phase III development this year. We look forward to sharing more details once these trials initiate. Our overarching goal is to create a weight management portfolio that addresses obesity and its interconnected conditions.
Sharon Barr: We are delighted to announce today that our once-daily oral GLP-1 receptor agonist, Ecoglipron, formerly known as AZD5004, met its primary endpoints in both the VISTA and SOLSTICE phase IIb trials conducted in people with obesity or type 2 diabetes, respectively. We look forward to sharing these data at the American Diabetes Association meeting in June. Based on the strength of these data, we are progressing Ecoglipron into phase III development this year. We look forward to sharing more details once these trials initiate. Our overarching goal is to create a weight management portfolio that addresses obesity and its interconnected conditions.
Speaker #5: We delighted are to announce today that our once GLP agonist , Alogliptin , formerly known as Azd5305 , met its primary in both the endpoints Vista Solstice Phase two trials and conducted in people with type or two diabetes , look forward American obesity at the respectively Association Diabetes meeting in .
Speaker #5: We are delighted to announce today that our once GLP agonist, Alogliptin, formerly known as AZD5305, met its primary endpoints in both the Vista and Solstice Phase 2 trials conducted in people with type 2 diabetes. We look forward to the American Diabetes Association data in June, respectively, for obesity and diabetes strength.
Speaker #5: Based on the data, we are progressing Alecko into phase three development. We look forward to sharing more details once trials initiate this year. Our overarching goal is to create a diversified weight portfolio that uniquely addresses obesity and its interconnected conditions. Our pipeline positions us to do this.
Sharon Barr: Our diversified pipeline uniquely positions us to explore innovative, novel combinations and, alongside Ecoglipron, we continue to advance our broader portfolio of different mechanisms, including a selective amylin receptor agonist, AZD6234, as a monotherapy and in combination with our dual GLP-1 glucagon receptor agonist, AZD9550, both of which are expected to deliver first phase II data this year. We also continue to invest in our earlier programs, augmented by recent external innovation to further strengthen our pipeline in this space. With that, please proceed to the next slide, and I'll pass over to Mark to cover rare disease.
Sharon Barr: Our diversified pipeline uniquely positions us to explore innovative, novel combinations and, alongside Ecoglipron, we continue to advance our broader portfolio of different mechanisms, including a selective amylin receptor agonist, AZD6234, as a monotherapy and in combination with our dual GLP-1 glucagon receptor agonist, AZD9550, both of which are expected to deliver first phase II data this year. We also continue to invest in our earlier programs, augmented by recent external innovation to further strengthen our pipeline in this space. With that, please proceed to the next slide, and I'll pass over to Mark to cover rare disease.
Speaker #5: explore combinations and Alecko , we continue to advance our management portfolio of different including a selective novel agonist . Azd6244 , alongside monotherapy and in innovative , combination mechanisms , dual Amylin GLP receptor receptor agonist .
Speaker #5: of which Azd9150 , are deliver expected to first phase two both this year . We also continue to our earlier programs , augmented by as a recent external one glucagon strengthen innovation , to our further in this .
Speaker #5: And with space data, please proceed to the slide, and I'll next pass investment over to Mark to cover disease pipeline rare.
Ruud Dobber: Thank you, Sharon. Can I get to the next slide, please? Rare Disease delivered total revenue of $9.1 billion in 2025, up 4% over the last year, driven by growth in neurology indications, increased patient demand, and continued global expansion. In the quarter, Ultomiris grew 15%, driven by patient demand across indications, including the competitive gMG and PNH markets. Soliris revenues continue to decline due to the successful conversion to Ultomiris, as well as biosimilar pressure. Strensiq grew 15% due to strong demand, with the quarter benefiting from tender order timing. We also saw strong underlying demand for Koselugo offset in the fourth quarter by order timing in certain tender markets. We continue to see great momentum across the Rare Disease portfolio, with further approvals for Koselugo and Ultomiris, expanding our geographic reach for these medicines.
Ruud Dobber: Thank you, Sharon. Can I get to the next slide, please? Rare Disease delivered total revenue of $9.1 billion in 2025, up 4% over the last year, driven by growth in neurology indications, increased patient demand, and continued global expansion. In the quarter, Ultomiris grew 15%, driven by patient demand across indications, including the competitive gMG and PNH markets. Soliris revenues continue to decline due to the successful conversion to Ultomiris, as well as biosimilar pressure. Strensiq grew 15% due to strong demand, with the quarter benefiting from tender order timing. We also saw strong underlying demand for Koselugo offset in the fourth quarter by order timing in certain tender markets. We continue to see great momentum across the Rare Disease portfolio, with further approvals for Koselugo and Ultomiris, expanding our geographic reach for these medicines.
Speaker #4: Thank you Sharon . And can I get to the next slide , please ? Rare disease delivered . revenue Total of $9.1 billion in 2025 , up 4% over the next last year , driven by growth in indications .
Speaker #4: Patient increased demand and continued global expansion in the quarter. Ultomiris grew, driven by 15% patient demand across indications, including the competitive and PNH, GMG; revenues continued to.
Speaker #4: Decline due to the successful conversion of Soliris to Tomyris, as well as biosimilar pressure. Strensiq grew 15% due to strong demand, with the quarter benefiting from tender or the timing.
Speaker #4: We also saw strong underlying demand for Koselugo, offset in the fourth quarter by other timing in certain tender markets. We continue to see great momentum across the rare disease portfolio, with further approvals for Koselugo and expanding our geographic Ultomiris reach for these medicines.
Ruud Dobber: Five years after announcing the acquisition, I am pleased to report that Alexion has delivered low double-digit compounded annual growth from 2020 to 2025 at constant exchange rates. We have also significantly expanded our global reach. At the time of the acquisition, Alexion medicines were available in 20 countries. By leveraging AstraZeneca footprint and the outstanding efforts of our teams, our life-changing rare disease therapies are now available in more than 75 countries worldwide. Finally, we have made meaningful progress in deepening scientific collaborations between AstraZeneca and Alexion researchers, further accelerating innovation. Our work across similar disease areas, such as the transthyretin cardiac amyloidosis or the development of our dual CD19 BCMA CAR-T across multiple therapeutic areas, are two evidences of this. This integrated approach enabled the seamless exchange of technologies and advancements across medicinal and process chemistry, molecular editing, and library platform.
Ruud Dobber: Five years after announcing the acquisition, I am pleased to report that Alexion has delivered low double-digit compounded annual growth from 2020 to 2025 at constant exchange rates. We have also significantly expanded our global reach. At the time of the acquisition, Alexion medicines were available in 20 countries. By leveraging AstraZeneca footprint and the outstanding efforts of our teams, our life-changing rare disease therapies are now available in more than 75 countries worldwide. Finally, we have made meaningful progress in deepening scientific collaborations between AstraZeneca and Alexion researchers, further accelerating innovation. Our work across similar disease areas, such as the transthyretin cardiac amyloidosis or the development of our dual CD19 BCMA CAR-T across multiple therapeutic areas, are two evidences of this. This integrated approach enabled the seamless exchange of technologies and advancements across medicinal and process chemistry, molecular editing, and library platform.
Speaker #4: Five years after announcing the, I am pleased to report that Alexion has now delivered low double-digit compounded annual growth from 2020 to 2025 at constant exchange rates.
Speaker #4: have We also significantly global expanded our reach time of the at the acquisition , Alexion medicines were in available 20 countries by leveraging AstraZeneca footprint and the outstanding efforts of our teams , our life rare disease therapies changing are now available in 75 countries worldwide .
Speaker #4: Finally , we have made meaningful in progress deepening scientific collaborations between AstraZeneca and Alexian researchers , further accelerating innovation . Our work similar across disease as areas such cardiac transthyretin , amyloidosis , or dual development of our Cd19 , the BCmA , Car-T across multiple therapeutic areas are to evidences of this .
Speaker #4: This integrated approach enables the seamless exchange of technologies and advancements across processed chemistry, medicinal and editing, and library molecular platforms. We now have more than 120 collaborative initiatives across AstraZeneca and Alexion, which are advancing our ambition to pioneer new treatments in our core therapeutic areas.
Ruud Dobber: We have now more than 120 collaborative initiatives across AstraZeneca and Alexion, which are advancing our ambition to pioneer new treatments and lead in our core therapeutic area. Please advance to the next slide. In 2026, we expect Ultomiris to grow, to continue to grow, driven primarily by neurology indication, including new-to-brain patients and those switching from Soliris, as well as further market expansions. We indicated peak your sales for Ultomiris to be above $5 billion, with contribution from both existing and new indications, such as HSCT-TMA, IgAN, and CSA-AKI. In the first half of the year, we anticipate high-level results in IgAN, where we have guided for the first endpoint at 34 weeks, assessing proteinuria. If positive, we will explore the potential for an accelerated approval in certain major markets. We also anticipate results from adult patients with HSCT-TMA.
Ruud Dobber: We have now more than 120 collaborative initiatives across AstraZeneca and Alexion, which are advancing our ambition to pioneer new treatments and lead in our core therapeutic area. Please advance to the next slide. In 2026, we expect Ultomiris to grow, to continue to grow, driven primarily by neurology indication, including new-to-brain patients and those switching from Soliris, as well as further market expansions. We indicated peak your sales for Ultomiris to be above $5 billion, with contribution from both existing and new indications, such as HSCT-TMA, IgAN, and CSA-AKI. In the first half of the year, we anticipate high-level results in IgAN, where we have guided for the first endpoint at 34 weeks, assessing proteinuria. If positive, we will explore the potential for an accelerated approval in certain major markets. We also anticipate results from adult patients with HSCT-TMA.
Speaker #4: Please area next slide advance to the . In 2026 , we expect Ultomiris to grow , to continue to grow , driven primarily by neurology indication , including new to brand those switching patients and from Soliris , as well as further market expansions .
Speaker #4: We indicated peak year sales for Ultomiris to be $5 billion , with contributions from both existing and new such as . indications Hsct-tma above , Igan and Csa-aki .
Speaker #4: In the first half of the year, we level anticipate high results in Igen, where we have guided for the first endpoint at 34 weeks, assessing proteinuria.
Speaker #4: positive , explore the If we will potential for accelerated approval in certain major an markets . We also anticipate results adult from patients with TMA .
Ruud Dobber: This data builds on a positive finding from the single-arm pediatric study completed in 2025. For Strensiq, we expect continued adoption supported by hypophosphatasia guidelines, which have led to increased disease awareness, diagnosis rates, and accelerated new patient starts. As global market expansion progresses, our priority remains advancing disease education to strengthen market readiness ahead of the readouts for eosinophil ALPHA, which we anticipate in the first half of 2026. Patient demand and geographic expansion in pediatric patients, in addition to the recent approval in adult patients, will continue to drive Koselugo's growth. We are well placed to deliver another year of strong performance supported by global demand for rare disease medicine, as well as meaningful indication expansion opportunities. Please advance to the next slide.
Ruud Dobber: This data builds on a positive finding from the single-arm pediatric study completed in 2025. For Strensiq, we expect continued adoption supported by hypophosphatasia guidelines, which have led to increased disease awareness, diagnosis rates, and accelerated new patient starts. As global market expansion progresses, our priority remains advancing disease education to strengthen market readiness ahead of the readouts for eosinophil ALPHA, which we anticipate in the first half of 2026. Patient demand and geographic expansion in pediatric patients, in addition to the recent approval in adult patients, will continue to drive Koselugo's growth. We are well placed to deliver another year of strong performance supported by global demand for rare disease medicine, as well as meaningful indication expansion opportunities. Please advance to the next slide.
Speaker #4: This data , built on a positive finding from the single arm pediatric study completed in 2025 for Strensiq . We expect continued adoption by Hypophosphatasia , supported guidelines , which have led to increased disease awareness , diagnosis rates and accelerated new patient starts global as expansion market priority progresses , our advancing remains education to market strengthen readiness ahead of the readouts for alpha , which we anticipate in first half the of 2026 .
Speaker #4: Demand and patient geographic expansion in pediatric patients, in addition to the recent approval in adult patients, will continue to drive Koselugo growth.
Speaker #4: We are well placed to deliver another year of strong performance, supported by global demand for rare disease medicine, as well as meaningful indication expansion opportunities.
Ruud Dobber: Our antibody-based depletion portfolio for cardiac and systemic amyloidosis continues to advance, with a focus on the two most prevalent forms of amyloidosis, transthyretin, and light chain. We announced the first phase III result last year for our most advanced pipeline candidate, Anselamimab. In the CARES phase III program, Anselamimab demonstrated a highly clinically meaningful improvement in both all-cause mortality and cardiovascular hospitalization in the subgroup of patients with kappa light chain amyloidosis. Global regulatory reviews and submissions are on the way. We have also expanded our collaboration with Neurimmune in December 2025 to include NI009, a fibril depleting antibody for the lambda light chain amyloidosis, which represents 80% of the light chain population and complements Anselamimab to address the broad patient population. We have accelerated development plan to move this molecule as quickly as possible into the clinic.
Ruud Dobber: Our antibody-based depletion portfolio for cardiac and systemic amyloidosis continues to advance, with a focus on the two most prevalent forms of amyloidosis, transthyretin, and light chain. We announced the first phase III result last year for our most advanced pipeline candidate, Anselamimab. In the CARES phase III program, Anselamimab demonstrated a highly clinically meaningful improvement in both all-cause mortality and cardiovascular hospitalization in the subgroup of patients with kappa light chain amyloidosis. Global regulatory reviews and submissions are on the way. We have also expanded our collaboration with Neurimmune in December 2025 to include NI009, a fibril depleting antibody for the lambda light chain amyloidosis, which represents 80% of the light chain population and complements Anselamimab to address the broad patient population. We have accelerated development plan to move this molecule as quickly as possible into the clinic.
Speaker #4: Please advance to the next slide on the antibody-based depletion portfolio for cardiac and systemic amyloidosis. Continue to advance with the focus on the two most prevalent forms of amyloidosis, transthyretin and light chain.
Speaker #4: We announced the first Phase 3 results last year. For the most advanced candidates in MAb, the CARES Phase 3 program on MAb demonstrated a highly clinically meaningful improvement in both all-cause mortality and cardiovascular hospitalization in the subgroup of patients with kappa light chain amyloidosis.
Speaker #4: Global regulatory reviews and submissions are on the way . We have also expanded our collaboration with Neurimmune . In December 25th . To include an I009 , febrile , a antibody for the light lambda chain , which amyloidosis represents 80% of the light chain population and on complement Mab to address the broad patient population .
Ruud Dobber: Coramitug, our first collaboration with Neurimmune, is now in phase III for ATTR-CM. The depletor trial completed enrollment, a full year ahead of plan, with more than 1,000 patients recruited. As Sharon mentioned, we also plan to initiate a phase IIB of our silencer Wainua with our depletor Coramitug, and we believe the combination of these two medicines has the potential to deliver a new standard of care for patients with ATTR-CM. The data generation to date reinforces our belief that targeted amyloid febril depletion with specific antibodies can significantly reduce mortality and hospitalization, transforming the course of the disease for these patients. And with that, please advance to the next slide, and I will hand back to Pascal. Thank you, Mark. Please next slide. As you can see here, the momentum of our pipeline continues not just in 2026 but also through to 2027.
Ruud Dobber: Coramitug, our first collaboration with Neurimmune, is now in phase III for ATTR-CM. The depletor trial completed enrollment, a full year ahead of plan, with more than 1,000 patients recruited. As Sharon mentioned, we also plan to initiate a phase IIB of our silencer Wainua with our depletor Coramitug, and we believe the combination of these two medicines has the potential to deliver a new standard of care for patients with ATTR-CM. The data generation to date reinforces our belief that targeted amyloid febril depletion with specific antibodies can significantly reduce mortality and hospitalization, transforming the course of the disease for these patients. And with that, please advance to the next slide, and I will hand back to Pascal. Thank you, Mark. Please next slide. As you can see here, the momentum of our pipeline continues not just in 2026 but also through to 2027.
Speaker #4: We have accelerated these plans to move molecule as development quickly as possible into the clinic. Our Neurimmune is in now with phase kilometres, first collaboration, three for ATTR.
Speaker #4: cardiomyopathy The trial Depleter , completed a full year enrollment plan ahead of with more than 1000 patients recruited as Sharon mentioned , to also plan initiate we phase two B of our silencer Wainua with our Depleter , and we believe the combination of these two medicines has the potential to a new deliver standard of care for patients with Attr cardiomyopathy .
Speaker #4: The data to date reinforces our belief that generation-targeted amyloid fibril depletion with specific antibodies can significantly reduce mortality and hospitalization, transforming the course of the disease.
Speaker #4: This is for patients. And with that, please advance to the next slide, and I will hand back to Pascal. Thank you.
Speaker #4: Mark. As you can see here, the slide of our pipeline momentum continues, not just in Q4, but also through to 2027.
Ruud Dobber: We have a significant number of high-value phase iii trials that can readout and support our growth to 2030 and beyond. In 2026 alone, the risk-adjusted combined peaker revenue opportunities in excess of $10 billion, as I said before, and again, the same in 2027. If we move to the next slide. In closing, we saw strong commercial momentum and great delivery across the pipeline in 2025, and our confidence in delivering the $80 billion ambition by 2030 is definitely increasing. With our broad portfolio in our deep pipeline, the meaningful progress we're making with our multiple transformation technologies, we can definitely reach this $80 billion ambition we have but also continue to grow past 2030. If we move to the next slide. Before we move to the Q&A, I want to thank Andy Barnett for his amazing contribution as head of investor relations over the last few years.
Ruud Dobber: We have a significant number of high-value phase iii trials that can readout and support our growth to 2030 and beyond. In 2026 alone, the risk-adjusted combined peaker revenue opportunities in excess of $10 billion, as I said before, and again, the same in 2027. If we move to the next slide. In closing, we saw strong commercial momentum and great delivery across the pipeline in 2025, and our confidence in delivering the $80 billion ambition by 2030 is definitely increasing. With our broad portfolio in our deep pipeline, the meaningful progress we're making with our multiple transformation technologies, we can definitely reach this $80 billion ambition we have but also continue to grow past 2030. If we move to the next slide. Before we move to the Q&A, I want to thank Andy Barnett for his amazing contribution as head of investor relations over the last few years.
Speaker #4: have a We significant number of high value three trials that can phase read out and support growth our to 2030 and beyond . And in 2026 alone , the risk adjusted combined revenue opportunities in excess of $10 billion .
Speaker #4: I said As and before same in 20 2727 , if we move to the next slide enclosing , we saw strong commercial momentum and great delivery across the pipeline .
Speaker #4: And in 2025, our confidence in delivering the $80 billion ambition by 2030 is definitely increasing, with our broad portfolio and our deep pipeline, and the meaningful progress we’re making. We’re undergoing multiple transformations with our Wecan technologies, which will definitely help us reach this $80 billion ambition we have, but also continue to grow past 2030. As we move to the next slide, before we move to the Q&A, I want to thank Andy Barnett for his amazing contribution as Head of Investor Relations over the last few years.
Ruud Dobber: I know he has enjoyed very much interacting with you, and I'm sure you have enjoyed interacting with him. He's very knowledgeable. He's a great guy, and he has a great sense of humor. So definitely a pleasure working with Andy, certainly for me and for the team, and I'm sure it was the case for you. I want to wish Andy great success in his new role as Country President for Japan. I'm sure he will make a great contribution to our company in Japan, just like he did to the IR function. I also want to welcome Joris, who must be somewhere in the room. Okay. Welcome, Joris. So Joris was, until recently, the Country President for the US Biopharma, and overall President Representative of AZ in the United States.
Ruud Dobber: I know he has enjoyed very much interacting with you, and I'm sure you have enjoyed interacting with him. He's very knowledgeable. He's a great guy, and he has a great sense of humor. So definitely a pleasure working with Andy, certainly for me and for the team, and I'm sure it was the case for you. I want to wish Andy great success in his new role as Country President for Japan. I'm sure he will make a great contribution to our company in Japan, just like he did to the IR function. I also want to welcome Joris, who must be somewhere in the room. Okay. Welcome, Joris. So Joris was, until recently, the Country President for the US Biopharma, and overall President Representative of AZ in the United States.
Speaker #4: I know he has enjoyed very much interacting with you—I'm sure you have, and enjoyed interacting with him. He's very knowledgeable.
Speaker #4: Great guy, and he has a great sense of humor. So, definitely a pleasure working with Andy for me. Suddenly, and with the team.
Speaker #4: And I'm sure it was the case. I— He's a— I want to wish Andy great success in his new role as country president. I'm sure he will make a great contribution to our company in Japan, not just to the IR function.
Speaker #4: I also want to welcome Iris , be the somewhere in room . Okay , welcome , Yuri . Yuri was , until recently , president country for for the US who must biopharma overall president and in the representative of AC United .
Ruud Dobber: Joris has driven tremendous growth throughout our company in the United States, in particular, built Farxiga to what it is, Fasenra, Tezspire, and really done a great job. Joris, before being in the US, worked in Asia, and so he has really great experience across Asia, the US, and Europe, and since he joined the company in 2000. So I'm sure Joris will also do a great job in IR, and I'm sure you'll enjoy working with him. So, as we move to the next slide, as Andy mentioned at the start of the call, please limit the number of questions you ask to allow everybody a fair chance to participate. And again, for those of you online, please use the raise hand function on Zoom. And with that, let's move to the first question. There are so many first questions. Over to you.
Ruud Dobber: Joris has driven tremendous growth throughout our company in the United States, in particular, built Farxiga to what it is, Fasenra, Tezspire, and really done a great job. Joris, before being in the US, worked in Asia, and so he has really great experience across Asia, the US, and Europe, and since he joined the company in 2000. So I'm sure Joris will also do a great job in IR, and I'm sure you'll enjoy working with him. So, as we move to the next slide, as Andy mentioned at the start of the call, please limit the number of questions you ask to allow everybody a fair chance to participate. And again, for those of you online, please use the raise hand function on Zoom. And with that, let's move to the first question. There are so many first questions. Over to you.
Speaker #4: And Iris has driven States tremendous growth throughout company in our in in the United States in particular , built for to what it is Fasenra Tezspire and really done a great job being in before the US .
Speaker #4: Worked in Asia so he . really has great And experience across Asia , the and US Europe . And since he joined the company in 2000 , so sure also do a I'm yours great job in IR .
Speaker #4: I'm sure And you'll enjoy working with So as if we him . move to the slide as Andy mentioned at the start of the call , please don't will please limit the number of questions ask to allow you fair everybody a chance to participate .
Speaker #4: And again , for those of you the please use raise online , to the Hand function on first question . let's move that , many .
Sharon Barr: Thank you, Pascal. So I've got two questions, please. I wanted to think a little bit about the growth beyond 2030, but it does connect to the readouts in 2026. You talked about the $10 billion risk-adjusted peak sales potential. Can you give us any more color on that, the mix of the $10 billion, the risk adjustments you've assumed, any assets in particular dominating the $10 billion? And should we assume higher success rates now for AstraZeneca after last year's strong performance? So that's the readouts this year and the link to the growth beyond 2030. And then I'd love to hear an update from Iskra on China. 2026, a lot of moving parts, but some good new launches and reimbursement going on as well.
[Analyst]: Thank you, Pascal. So I've got two questions, please. I wanted to think a little bit about the growth beyond 2030, but it does connect to the readouts in 2026. You talked about the $10 billion risk-adjusted peak sales potential. Can you give us any more color on that, the mix of the $10 billion, the risk adjustments you've assumed, any assets in particular dominating the $10 billion? And should we assume higher success rates now for AstraZeneca after last year's strong performance? So that's the readouts this year and the link to the growth beyond 2030. And then I'd love to hear an update from Iskra on China. 2026, a lot of moving parts, but some good new launches and reimbursement going on as well.
Speaker #4: First questions, you over to.
Speaker #6: You. Thank you. So, Pascal, I've got two questions, please. I wanted to think a little bit about the growth beyond 2030, but it does connect to the readouts in 2026.
Speaker #6: You talked about the $10 billion risk-adjusted peak potential. Can you give us any more color on that? The mix of the $10 billion, the risk adjustments on it—any assets in particular dominating that—should we think of the $10 billion in a certain way?
Speaker #6: Higher assume rates now for AstraZeneca success after last year's strong performance. So that's readouts this year, and they link the growth to the years beyond 2030.
Speaker #6: And then I'd love to hear an update from Iskra on China 2026. A lot of moving parts, but some good news.
Sharon Barr: So just an update there on how we should think about 2026 and perhaps some color on profitability of China versus history versus the rest of the group. Thank you.
[Analyst]: So just an update there on how we should think about 2026 and perhaps some color on profitability of China versus history versus the rest of the group. Thank you.
Speaker #6: Launches and reimbursement going on as well. And so, just update there how we should think about '26 and some color, perhaps, on the profitability of China versus history, versus the rest of the group.
Pascal Soriot: Thank you. Iskra, do you want to cover the second one? And maybe for the first one, we'll have to get input from a number of people there. But go ahead, Iskra, to start.
Pascal Soriot: Thank you. Iskra, do you want to cover the second one? And maybe for the first one, we'll have to get input from a number of people there. But go ahead, Iskra, to start.
Speaker #6: Thank of the
Speaker #6: Thank you. Thank you.
Speaker #4: You, do cover the second one, and maybe for the first one we'll have to get input from a number of people there.
Iskra Reic: Thanks, Luisa, for the question. So let me start by saying that we are very happy to see the strong performance in China in 2025, and it definitely gives us confidence.
Iskra Reic: Thanks, Luisa, for the question. So let me start by saying that we are very happy to see the strong performance in China in 2025, and it definitely gives us confidence.
Speaker #4: ahead to start
Speaker #4: .
Speaker #7: question . So let me Thanks start by saying that we are very happy to see the strong performance in China in 25 , and it definitely gives us a confidence .
Pascal Soriot: Can you speak in the microphone? It's probably hard.
Pascal Soriot: Can you speak in the microphone? It's probably hard.
Iskra Reic: I have it here, but I don't know whether it works. So let me try. Is it better now? Yeah. I don't know. It definitely gives confidence in the outlook of 2026. Now, when you think about 2026 in China, I think there are two main components. One is obviously the headwind of the VBP for Farxiga, Roxadustat, and Lynparza. And as we have always seen, there are expectations of the decline post-VBP that is driven by both price decrease as well as volume reduction. But when it comes specifically to Farxiga, I do believe that we can also expect the brand recovery in the midterm. And we saw the similar trend with Brilinta and Crestor in the past. And it is really driven by the strong brand perception, strong brand loyalty, and recovery specifically in the retail channel.
Iskra Reic: I have it here, but I don't know whether it works. So let me try. Is it better now? Yeah. I don't know. It definitely gives confidence in the outlook of 2026. Now, when you think about 2026 in China, I think there are two main components. One is obviously the headwind of the VBP for Farxiga, Roxadustat, and Lynparza. And as we have always seen, there are expectations of the decline post-VBP that is driven by both price decrease as well as volume reduction. But when it comes specifically to Farxiga, I do believe that we can also expect the brand recovery in the midterm. And we saw the similar trend with Brilinta and Crestor in the past. And it is really driven by the strong brand perception, strong brand loyalty, and recovery specifically in the retail channel.
Speaker #4: Can you speak on the microphone? It's hard. Okay.
Speaker #7: I don't know what works, so let me try. Is it better now, whether it—I don't know. It definitely gives a confidence in the—
Speaker #7: of 26 . outlook Now when you think about 26 in Yeah I China I think there are two main components . One is obviously the headwind of the of the vwbp for for Sega and and , Roxadustat Lynparza .
Speaker #7: as , as we have And a seen , already expectations of the there is post decline DVP that is both driven by price decrease as well as well as volume reduction .
Speaker #7: But when it comes specifically to for Sega , I can do also believe that we brand recovery expect the in the we saw the similar trend with the the Crestor in past Betaloc and , and it is really driven by the strong brand perception , brand brand strong loyalty and recovery retail channel , specifically .
Iskra Reic: When it comes to the tailwinds in China, we feel very confident that we will continue to see the growth of the new launches, specifically driven by our success of including Fasenra through VBP and Calquence tablets in the NRDL starting 1 January 2024. When you think about the Imfinzi performance post-NRDL, and Dave mentioned that in his presentation, we saw very strong uptake. Our ability to include Imfinzi in the more than 1,000 hospital listings in less than a quarter gives us confidence that we will be able to see the successful launches going forward. When it comes to the profitability, profitability in China is still lower than the group.
Iskra Reic: When it comes to the tailwinds in China, we feel very confident that we will continue to see the growth of the new launches, specifically driven by our success of including Fasenra through VBP and Calquence tablets in the NRDL starting 1 January 2024. When you think about the Imfinzi performance post-NRDL, and Dave mentioned that in his presentation, we saw very strong uptake. Our ability to include Imfinzi in the more than 1,000 hospital listings in less than a quarter gives us confidence that we will be able to see the successful launches going forward. When it comes to the profitability, profitability in China is still lower than the group.
Speaker #7: When it comes to the tailwinds in China, we feel very confident that we will continue to see the growth of the new launches, specifically driven by our success of including Fasenra and Calquence Cup tablets in the through needle, 1st of January this year.
Speaker #7: When starting about Enhertu for performance, you think, and they saw the presentation. We, his, mentioned that in very strong, and our uptake ability includes Enhertu in more than 1,000 hospital listings. In the, in the, than less a, than a quarter, gives us confidence that we are able to, will be successful, see the launches going forward.
Iskra Reic: But I think you always need to think about the huge volume, huge unmet need, and opportunity there and put that in the perspective of a bit lower prices than in the rest of the world.
Iskra Reic: But I think you always need to think about the huge volume, huge unmet need, and opportunity there and put that in the perspective of a bit lower prices than in the rest of the world.
Speaker #7: When it comes to the profitability . Profitability in China is still lower than the group . But I think you always the than always need to think about the huge volume and huge need .
Speaker #7: And opportunity there and put unmet that in the in the perspective of the the of a bit lower prices than in the rest of the world .
Pascal Soriot: Your first question had two sub-questions, really. And then the second sub-question was about success rate. And I wish that we continue experiencing the same success rate, but I don't think we can promise this because, as you know, the risk is part of our industry, really. And we have to brace and accept the fact that we actually will experience failures. Now, having said that, I'd like to ask maybe Susan to do two things. One is to talk about the joint venture, the project we are working together with Tempus on, and using AI and multimodal model to actually help improve the probability of success in our studies and better shape them.
Pascal Soriot: Your first question had two sub-questions, really. And then the second sub-question was about success rate. And I wish that we continue experiencing the same success rate, but I don't think we can promise this because, as you know, the risk is part of our industry, really. And we have to brace and accept the fact that we actually will experience failures. Now, having said that, I'd like to ask maybe Susan to do two things. One is to talk about the joint venture, the project we are working together with Tempus on, and using AI and multimodal model to actually help improve the probability of success in our studies and better shape them.
Speaker #7: .
Speaker #4: And your first question , had like two sub questions really . And then the second was about success rate . And I wish that we continue experiencing the same success rate .
Speaker #4: But I think we don't can promise this as you the because risk is part of our industry really . And we have to embrace and accept the brace for the fact that we actually will experience failures .
Speaker #4: Now, having said that, I'd maybe ask Susan to do two things. One is I'd like to ask her to talk about the joint venture, the project.
Speaker #4: Are we working with Tempus and together using AI and multimodal models to actually help improve the success probability of studies and better shape them?
Pascal Soriot: So, you can sort of give a little bit of highlights on this and then comment on what are the two or three big projects, not too many, two or three big projects you think will drive growth in oncology/hematology?
Pascal Soriot: So, you can sort of give a little bit of highlights on this and then comment on what are the two or three big projects, not too many, two or three big projects you think will drive growth in oncology/hematology?
Speaker #4: So you can sort of give a little bit of then this . highlights on And what are on the projects . 2 or 3 big Not too comment many , 2 or 3 big you think will projects drive growth in oncology , hematology ?
[Company Representative] (AstraZeneca): Yeah. Thanks, Pascal. So my reflection, if you like, of the last decade in oncology about the success rates we've had has been predicated on being able to identify the right patient populations to treat. You've seen that. That's been important with Lynparza. It's been important with Tagrisso. I think that continues to be something that's important. The foundation model work that we've got with Tempus Pathos, the ambition is that we'll have the largest multimodal foundation model that will take the unstructured data that's in patient records, the lab data, the genomics data, transcripts-only data where available, imaging, and pathology, and integrate all of that into the largest foundation model for oncology because of the large dataset that we have with Tempus and Pathos.
[Company Representative] (AstraZeneca): Yeah. Thanks, Pascal. So my reflection, if you like, of the last decade in oncology about the success rates we've had has been predicated on being able to identify the right patient populations to treat. You've seen that. That's been important with Lynparza. It's been important with Tagrisso. I think that continues to be something that's important. The foundation model work that we've got with Tempus Pathos, the ambition is that we'll have the largest multimodal foundation model that will take the unstructured data that's in patient records, the lab data, the genomics data, transcripts-only data where available, imaging, and pathology, and integrate all of that into the largest foundation model for oncology because of the large dataset that we have with Tempus and Pathos.
Speaker #3: Yeah . Thanks , Pascal . So you know , my reflection , if you like , the the of last decade in oncology about the success rates we've had has been being able to predicated on identify the right patient populations to treat .
Speaker #3: You've seen that that's been important with Lynparza. With Tagrisso, it's been important as well. I think that continues to be something that's important.
Speaker #3: Important model foundation work that we got Tempus with pathos, then we'll have the ambition is that largest multimodal foundation tech model, that data that's unstructured will in records patient.
Speaker #3: data lab The , the genomics data , transcriptomic data where where available imaging and pathology and integrate all of into the that largest foundation model oncology for of the .
[Company Representative] (AstraZeneca): The hope is, I mean, what we've already been doing is using those kinds of real-world evidence datasets to both help design our phase III trials and predict what the control arm performance is going to be, particularly when you're going in with a new biomarker. You don't necessarily have the historical literature data, but if you can benchmark that using these data, it's helpful. So the idea is that you would reduce the uncertainty in both the design and the prediction of outcome of phase III trials by using these foundation models. The hope is also that you could better identify the patient populations where the biology is a little more complicated. So we're still relying, for example, on PD-L1 in the IO space as the only biomarker that has really broadly been uptaken, and everybody is aware that that is imperfect.
[Company Representative] (AstraZeneca): The hope is, I mean, what we've already been doing is using those kinds of real-world evidence datasets to both help design our phase III trials and predict what the control arm performance is going to be, particularly when you're going in with a new biomarker. You don't necessarily have the historical literature data, but if you can benchmark that using these data, it's helpful. So the idea is that you would reduce the uncertainty in both the design and the prediction of outcome of phase III trials by using these foundation models. The hope is also that you could better identify the patient populations where the biology is a little more complicated. So we're still relying, for example, on PD-L1 in the IO space as the only biomarker that has really broadly been uptaken, and everybody is aware that that is imperfect.
Speaker #3: large data set that we have us with Because and pathos what we've been doing is is , I mean , already using those kinds of , the hope real world evidence data sets to both help design our phase three trials and what predict the control arm going to be when you're going , particularly in with a new .
Speaker #3: you don't You know , necessarily have the historical literature if you can benchmark that data , but data , these it's helpful . idea is that you would So the reduce the uncertainty in both the design and the prediction of outcome of phase three trials .
Speaker #3: By using foundation models, the hope is also that you could better identify the patient where the population's biology is a little more complicated.
Speaker #3: So we're for relying , still on the I Pd-l1 o space as the only really been biomarker that And broadly aware that that is imperfect .
[Company Representative] (AstraZeneca): So I think this technology can really help in those spaces, still to be proven, but I'm optimistic that that can make a difference.
[Company Representative] (AstraZeneca): So I think this technology can really help in those spaces, still to be proven, but I'm optimistic that that can make a difference.
Speaker #3: So I think everybody thinks this technology can really help spaces. In those, still to be proven. But I’m optimistic that a difference can be made.
Pascal Soriot: Dave, do you want to cover the second part?
Pascal Soriot: Dave, do you want to cover the second part?
[Company Representative] (AstraZeneca): Yeah, just on the second.
[Company Representative] (AstraZeneca): Yeah, just on the second.
Pascal Soriot: And then, Ruud, if you could also talk about a couple of products in biopharma that would drive growth.
Pascal Soriot: And then, Ruud, if you could also talk about a couple of products in biopharma that would drive growth.
Dave Fredrickson: So Luisa said very specifically on the readouts that Pascal went through, Emerald III is a blockbuster-plus opportunity in HDC, and I think builds off of a program that has currently success with Imfinzi. Certainly, when you take a look at data across AVANZAR 07, that is for just the AZ share alone, multi-blockbuster opportunity if those studies are positive, and we've got an opportunity to move forward with that. SERENA IV is multi-blockbuster in terms of the opportunity that it represents. And then lastly, PAC-9. We don't talk a lot about PAC-9, but I think PAC-9, if that study were to come through, gives an opportunity to actually build off of our Pacific leadership where we've been able to enjoy a space without having much competition coming into the area. So those are the highlights I'd hit.
Dave Fredrickson: So Lisa said very specifically on the readouts that Pascal went through, Emerald III is a blockbuster-plus opportunity in HDC, and I think builds off of a program that has currently success with Imfinzi. Certainly, when you take a look at data across AVANZAR 07, that is for just the AZ share alone, multi-blockbuster opportunity if those studies are positive, and we've got an opportunity to move forward with that. SERENA IV is multi-blockbuster in terms of the opportunity that it represents. And then lastly, PAC-9. We don't talk a lot about PAC-9, but I think PAC-9, if that study were to come through, gives an opportunity to actually build off of our Pacific leadership where we've been able to enjoy a space without having much competition coming into the area. So those are the highlights I'd hit.
Speaker #4: Dave , do you want to cover the second part ? Yeah , just on the second , row . If you could also talk about of products in a couple would drive Biopharm that growth .
Speaker #2: So a very specifically on the readouts Pascal went that through , Emerald three is a blockbuster plus opportunity in HCC , think and I builds off of a program that has currently success within Finzi .
Speaker #2: Certainly take a look at when you data across Avanzar oh seven , that is for just the A-Z share alone , multi opportunity .
Speaker #2: Those studies, if blockbuster positive, and we've got opportunity to and are forward move for is multi. Of the it, Serena represents opportunity that, then lastly, pack nine.
Speaker #2: Those studies, if blockbuster positive, and we’ve got opportunity to— and our forward move for is multi. Of it, Serena represents opportunity, then lastly.
Speaker #2: About pack nine. But I think pack nine, if that study were to come, and through it gives us the opportunity actually to build off—we've talked a lot—been able to do much without having competition in the space, in that area.
Pascal Soriot: Yeah, and a few highlights from a biopharma perspective. Lorundrostat, our oral PCSK9, we're going to expect the first dataset in the course of 2027. It's, in our view, a very high potential, potentially a $5 billion-plus potential. Clearly, Baxdrostat I'm sure many more questions about Baxdrostat not only the monocomponent but also the combination, I think, with the SGLT2. Dapagliflozin is a very important one. And then the other two combinations, Balcinrenone and DAPA in kidney disease and heart failure, where there's a high metabolic need. And the combination of Zibotentan with Dapagliflozin has a sales potential between $3 and 5 billion. So there are a couple of big products. And then, of course, the bonus will be potentially Tozorakimab, as mentioned by Sharon. There's a high metabolic need still in the COPD space.
Pascal Soriot: Yeah, and a few highlights from a biopharma perspective. Lorundrostat, our oral PCSK9, we're going to expect the first dataset in the course of 2027. It's, in our view, a very high potential, potentially a $5 billion-plus potential. Clearly, Baxdrostat I'm sure many more questions about Baxdrostat not only the monocomponent but also the combination, I think, with the SGLT2. Dapagliflozin is a very important one. And then the other two combinations, Balcinrenone and DAPA in kidney disease and heart failure, where there's a high metabolic need. And the combination of Zibotentan with Dapagliflozin has a sales potential between $3 and 5 billion. So there are a couple of big products. And then, of course, the bonus will be potentially Tozorakimab, as mentioned by Sharon. There's a high metabolic need still in the COPD space.
Speaker #2: Enjoy. So those are the highlights. I'd hit.
Speaker #8: Yeah , and a few biopharma perspective . Lara prostate , highlights from a our oral Pcsk9 . We're going to expect the first data set in the course of 2027 is , in our a very high view , potential , $5 billion plus potential stat , .
Speaker #8: sure many more about Dextrostat not only the Monocomponent , the combination . but also I think with with the Sglt2 dapagliflozin is a And then very important one .
Speaker #8: The other two combinations, belzutifan and DAPA in kidney disease, have potential where heart risk is high. And the need for the zibotentan combination with dapagliflozin has a sales failure potential. So there are a couple of big ones between $3 billion and $5 billion.
Speaker #8: products. And then, of course, bonus will be potentially to the torso. As mentioned by Sharon, it is a medical need—COPD is still in the space.
Pascal Soriot: If the product is hitting the TPP, I firmly believe that this will be a multi-billion-dollar opportunity as well. How about we stay on this table? But please, one question. I'll pick one question and keep the second one if you have a second one for later.
Pascal Soriot: If the product is hitting the TPP, I firmly believe that this will be a multi-billion-dollar opportunity as well. How about we stay on this table? But please, one question. I'll pick one question and keep the second one if you have a second one for later.
Speaker #8: Product is hitting the TPP. I firmly believe that this will be a multi-billion dollar opportunity as well.
James Gordon: Yep. Thanks, Pascal. Richard Vosser from J.P. Morgan. Maybe thoughts on the implications of the LYDIA result over to the SERENA-4 trial in terms of design. Susan, you mentioned choosing the right patient population. Just thoughts on what you've done in SERENA-4 on the back of the LYDIA result. Maybe if I can sneak it, thoughts on CAMBRIA-1 as well, given what LYDIA does that impact the commerciality? But Pascal, ignore that if that is two.
Richard Vosser: Yep. Thanks, Pascal. Richard Vosser from J.P. Morgan. Maybe thoughts on the implications of the LYDIA result over to the SERENA-4 trial in terms of design. Susan, you mentioned choosing the right patient population. Just thoughts on what you've done in SERENA-4 on the back of the LYDIA result. Maybe if I can sneak it, thoughts on CAMBRIA-1 as well, given what LYDIA does that impact the commerciality? But Pascal, ignore that if that is two.
Speaker #4: How about we stay on this table for now, please? I'll pick the second one to keep, and have one question—just one question. If you have a second one, keep it for later.
Speaker #6: Thanks, Pascal. From JP, Rich Morgan.
Speaker #6: idea of the . Over to the Serena In terms of ? design . Result you mentioned for trial . choosing patient population thoughts on . .
Speaker #6: idea of the . Over to the Serena In terms of ? design . Result you mentioned for trial . choosing patient population thoughts on .
Speaker #6: done in the right Serena for on the back on the result . And of the maybe if I Just can it sneak . Thoughts on Cambria Lidia one as well .
Pascal Soriot: No, no. We'll grant you the second one because it's still related to Cambria anyway. So over to you, Susan.
Pascal Soriot: No, no. We'll grant you the second one because it's still related to Cambria anyway. So over to you, Susan.
Speaker #6: Given what Lidia just does, that—yeah. Impact the commerciality? But Pascal, ignore that if true.
[Company Representative] (AstraZeneca): Okay. All right. So I mean, I think what we've now seen is proof, as we've been saying consistently, that SERDs, because of the mechanism of action of both full antagonism and inhibition of estrogen receptor but also degradation, can have activity not just in the ESR1 mutant but in the endocrine-sensitive ESR1 wild type. And I think you've seen that. We've been saying it for a while. But when you look at the second line setting, that is less endocrine-sensitive, and so the effect size has been smaller there. So the basis of SERENA-4's confidence is that we have tried to design the study to enrich for the endocrine-sensitive components of the first line setting. That's based on recruiting patients with recurrence and early-stage disease after at least two years of adjuvant therapy because those that are less endocrine-sensitive will progress more rapidly than that.
Susan Galbraith: Okay. All right. So I mean, I think what we've now seen is proof, as we've been saying consistently, that SERDs, because of the mechanism of action of both full antagonism and inhibition of estrogen receptor but also degradation, can have activity not just in the ESR1 mutant but in the endocrine-sensitive ESR1 wild type. And I think you've seen that. We've been saying it for a while. But when you look at the second line setting, that is less endocrine-sensitive, and so the effect size has been smaller there. So the basis of SERENA-4's confidence is that we have tried to design the study to enrich for the endocrine-sensitive components of the first line setting. That's based on recruiting patients with recurrence and early-stage disease after at least two years of adjuvant therapy because those that are less endocrine-sensitive will progress more rapidly than that.
Speaker #4: I
Speaker #4: grant you the second one because it's still related to anyway . me So over will to you , Susan . Okay . All right .
Speaker #3: So that is I mean , I think what we've now seen is , is proof , as we've been saying consistently , that that thirds of mechanism action , , because of the are both full and inhibition antagonism of estrogen also degradation receptor .
Speaker #3: But the esr1 mutant , but in the ESL I think type . you've been saying that . you've seen second line , the setting that is less less sensitive , and effect size so the there .
Speaker #3: So, the than basis of confidence smaller, has been we have design the tried to study enrich for the endocrine sensitive to of the of the first line components setting.
Speaker #3: That's based on recruiting recurrence in stage disease. After two years of adjuvant extended with — because those patients that are therapy progress less sensitive will more rapidly than that, at least 12 months must have elapsed since the patient's last of the adjuvant dose then.
[Company Representative] (AstraZeneca): At least 12 months must have elapsed since the patient's last dose of the adjuvant AI. Then there's some patients with de novo stage IV disease. So these are clinical features that are enriched to enrich for that endocrine-sensitive patient population. Of course, what you've also got is potentially the prevention of emergence of ESR1 mutations because you are essentially blocking that clonal selection drive because of the mechanism of action. So that's what underpins our confidence in serena-4. And I think having seen the fact that you've got activity in an adjuvant setting in an endocrine-sensitive population increases the confidence in that. But obviously, there's still those trial design features. And of course, it's in combination with a CDK4/6 inhibitor.
Susan Galbraith: At least 12 months must have elapsed since the patient's last dose of the adjuvant AI. Then there's some patients with de novo stage IV disease. So these are clinical features that are enriched to enrich for that endocrine-sensitive patient population. Of course, what you've also got is potentially the prevention of emergence of ESR1 mutations because you are essentially blocking that clonal selection drive because of the mechanism of action. So that's what underpins our confidence in serena-4. And I think having seen the fact that you've got activity in an adjuvant setting in an endocrine-sensitive population increases the confidence in that. But obviously, there's still those trial design features. And of course, it's in combination with a CDK4/6 inhibitor.
Speaker #3: . Some patients that And with de at least stage four novo clinical disease . these are So features that are to enrich for endocrine that sensitive enriched patient population .
Speaker #3: Of course, also is the potential prevention of emergence of ESR1 mutations, because you are essentially blocking that clonal selection, what you've driven because of the GOT mechanism of action.
Speaker #3: So, underpins confidence, our— And I think, Serena, for having seen the fact of that; you've actually got adjuvant activity in an endocrine-sensitive population, in an adjuvant setting, that increases the endocrine.
Speaker #3: But obviously that's what the still the trial design and of course in combination with features Cdk4 point out six inhibitor . I would your second question , it's So Cambria one .
[Company Representative] (AstraZeneca): To your second question about CAMBRIA-1, again, I would just point out that we're the only company that has two adjuvant studies with our SERD, one designed for the patient population after two to five years of CDK4/6, which is CAMBRIA-1, and the other for the patient population newly diagnosed, which is CAMBRIA-2. That gives us the opportunity to be able to, if we're successful, to access the largest group of patients in the adjuvant setting from those two different patient populations. And of course, the other difference is that we are allowing a combination with abemaciclib, which is going to be very relevant as the data continue to mature for CDK4/6 in the adjuvant setting. So I think that was the basis of the trial design that we had.
Susan Galbraith: To your second question about CAMBRIA-1, again, I would just point out that we're the only company that has two adjuvant studies with our SERD, one designed for the patient population after two to five years of CDK4/6, which is CAMBRIA-1, and the other for the patient population newly diagnosed, which is CAMBRIA-2. That gives us the opportunity to be able to, if we're successful, to access the largest group of patients in the adjuvant setting from those two different patient populations. And of course, the other difference is that we are allowing a combination with abemaciclib, which is going to be very relevant as the data continue to mature for CDK4/6 in the adjuvant setting. So I think that was the basis of the trial design that we had.
Speaker #3: company the only just that with studies our has Again patient the population , one designed for 2 to 5 years age , Cambria other for the two adjuvant patient newly one and the diagnosed , which is Cambria two , which is that gives us the opportunity population , to to be of able , after if we're successful , to access the group of patients in the adjuvant two different those setting from patient populations .
Speaker #3: largest continue In the setting . basis of the trial I think that design that we had . And we're optimistic that those trials was the will read positive out given proof of principle .
Speaker #3: And of course , the other difference is that we are combination allowing abemaciclib , which is with , you be very know , going to the data relevant as to mature for adjuvant Cdk4 six .
[Company Representative] (AstraZeneca): We're optimistic that those trials will read out positive given proof of principle, if you like, that this class can have a difference there.
Susan Galbraith: We're optimistic that those trials will read out positive given proof of principle, if you like, that this class can have a difference there.
Pascal Soriot: Next. We just finished this table, but.
Pascal Soriot: Next. We just finished this table, but.
James Gordon: I think I've got the mic, Pascal, if I can. It's Matthew Weston from UBS.
Matthew Weston: I think I've got the mic, Pascal, if I can. It's Matthew Weston from UBS.
Speaker #3: If you like, then this is the difference. So, class...
Speaker #3: .
Pascal Soriot: Oh, Matthew. Sorry. Go ahead.
Pascal Soriot: Oh, Matthew. Sorry. Go ahead.
Speaker #4: We
James Gordon: One question, please, on Ecoglipron, if I can. You've made the announcement that you're moving to phase III, which I assume indicates confidence in the phase II profile that you've seen. But I could read that two ways because you also have a unique target product profile, I think, in phase III because you're looking about weight management in combination with other parts of your cardiovascular portfolio. So can you make some comments as to whether or not, for you, being confident to drive that move to phase III means that you think you have efficacy at least as good or better than the competition, or whether or not you think that it meets your target product profile of at least achieving modest weight loss, which you can then use in combination with other agents?
Matthew Weston: One question, please, on Ecoglipron, if I can. You've made the announcement that you're moving to phase III, which I assume indicates confidence in the phase II profile that you've seen. But I could read that two ways because you also have a unique target product profile, I think, in phase III because you're looking about weight management in combination with other parts of your cardiovascular portfolio. So can you make some comments as to whether or not, for you, being confident to drive that move to phase III means that you think you have efficacy at least as good or better than the competition, or whether or not you think that it meets your target product profile of at least achieving modest weight loss, which you can then use in combination with other agents?
Speaker #4: But .
Speaker #6: think .
Speaker #9: The mic I’ve got—can I...
Speaker #9: Matthew I. It's UBS.
Speaker #9: Westin
Speaker #9: Westin
Speaker #4: Sorry . Go
Speaker #9: please . from On . if I can . You've made announcement that the you're moving three , to phase which I ahead assume the confidence in seen phase two you've I could that two ways read , because you also have unique target product a profile .
Speaker #9: . think But in phase three , because about weight management you're looking combination parts with other of your cardiovascular portfolio . So can some comments as to whether or not for you being drive that confident to move to phase three means that you think you have efficacy .
Speaker #9: least as the competition , or whether or At not you think your target that it product meets profile . Of at least achieving modest weight loss , then use in combination with other which you can agents .
Pascal Soriot: Let me just answer this one because it's easy to answer, actually. It is. We would never move a product in phase III and unleash the kind of spend we are committing to if we didn't think we have a product with a competitive profile. So I think the short answer to your question is we believe we have a very competitive profile, and it doesn't rely on combinations. It actually relies on the monotherapy itself. And of course, combination comes on top. But if monotherapy was not competitive, it would be hard to move it into phase III and unlock so much investment.
Pascal Soriot: Let me just answer this one because it's easy to answer, actually. It is. We would never move a product in phase III and unleash the kind of spend we are committing to if we didn't think we have a product with a competitive profile. So I think the short answer to your question is we believe we have a very competitive profile, and it doesn't rely on combinations. It actually relies on the monotherapy itself. And of course, combination comes on top. But if monotherapy was not competitive, it would be hard to move it into phase III and unlock so much investment.
Speaker #4: Let me answer this one, because it's actually easy to answer. We would never move a product into phase three and unleash the kind of spend we have.
Speaker #4: We me just to are didn't think we . have a committing If we product with profile , competitive a so the short question I think is believe we have we a very it rely doesn't combinations profile and competitive .
Speaker #4: It the on actually relies on monotherapy itself combination course , comes on top . monotherapy was . not But if it would And of to move into phase three .
James Gordon: I think I've got the microphone.
Matthew Weston: I think I've got the microphone.
Pascal Soriot: Are you? Maybe James?
Pascal Soriot: Are you? Maybe James?
James Gordon: Great. Thanks a lot. James and Bart, please. One of the phase III readouts in the first half is asfotase alfa, which I think had been badged as a $3 to 5 billion opportunity, but I'm aware there's three different trials. So is it a all-or-nothing to get the $3 to 5 billion, or are there scenarios where some trials are more or less successful? And how would that break down?
[Company Representative]: Great. Thanks a lot. James and Bart, please. One of the phase III readouts in the first half is asfotase alfa, which I think had been badged as a $3 to 5 billion opportunity, but I'm aware there's three different trials. So is it a all-or-nothing to get the $3 to 5 billion, or are there scenarios where some trials are more or less successful? And how would that break down?
Speaker #4: And it unlocks so much in investment. Maybe.
Speaker #6: Great .
Speaker #10: Thanks a lot. Barclays, James from.
Speaker #10: readouts in the phase three Azimuts first half is Alpha , which I think had a of the 3 to 5 billion opportunity . been Jameson based as trials .
Speaker #10: there's three different a all or nothing aware to get or are the 3 to 5 billion , the But I'm scenarios where trials are more or less successful ?
Iskra Reic: Yeah. So thank you for asking the question. As you are mentioning, there are three trials. There are two trials in the pediatric population where Strensiq was originally approved. One of these trials is a switch from Strensiq to a synthetase. There is another trial in the pediatric population in the naïve, in the Strensiq naïve population against placebo. And the third trial combines both adolescent and adult. You know that the label of Strensiq, depending on the jurisdiction, is usually focusing on the pediatric population. And sometimes, we have adult with pediatric onset in the label. But the intent of the synthetase program was to test in the totality of the population from pediatric, adolescent, adult, and even adult of a certain age, if I may say.
Pascal Soriot: Yeah. So thank you for asking the question. As you are mentioning, there are three trials. There are two trials in the pediatric population where Strensiq was originally approved. One of these trials is a switch from Strensiq to a synthetase. There is another trial in the pediatric population in the naïve, in the Strensiq naïve population against placebo. And the third trial combines both adolescent and adult. You know that the label of Strensiq, depending on the jurisdiction, is usually focusing on the pediatric population. And sometimes, we have adult with pediatric onset in the label. But the intent of the synthetase program was to test in the totality of the population from pediatric, adolescent, adult, and even adult of a certain age, if I may say.
Speaker #10: And how down break ?
Speaker #11: Yeah .
Speaker #11: thank you for asking question there . the you as you As are mentioning , there are three trials . two trials So are in the pediatric population There
Speaker #11: Where that was originally approved, trials are from Strensiq switch to Fortes. There is a trial in the pediatric population, and another in a naive population. One of these Strensiq-naive population trials, against placebo, combines both adolescent and adult groups.
Speaker #11: and You know label of that the strensiq , depending on the jurisdiction , usually is focusing on the Strensiq pediatric population and sometimes we have adult with pediatric onset in the in the label .
Speaker #11: But the intent of the Fortes program was to test in the totality of the population, from adolescents and even adults over a certain age.
Iskra Reic: So this is what this program of 1850 covers so that we would know the answer to the question we've been asking a lot about Strensiq. And we are now expecting the results in the first half of 2026. And we'll put all this together. And hopefully, we'll be able to submit for a product that is much easier, another enzyme therapy product but much easier to utilize than Strensiq, which has to be administered every day or every other day, which, of course, is very cumbersome. So this product would be provided once every other week. It would provide a great benefit. And if we demonstrate efficacy and safety in the total population, this would make asfotase alfa a product several times the value of Strensiq.
Pascal Soriot: So this is what this program of 1850 covers so that we would know the answer to the question we've been asking a lot about Strensiq. And we are now expecting the results in the first half of 2026. And we'll put all this together. And hopefully, we'll be able to submit for a product that is much easier, another enzyme therapy product but much easier to utilize than Strensiq, which has to be administered every day or every other day, which, of course, is very cumbersome. So this product would be provided once every other week. It would provide a great benefit. And if we demonstrate efficacy and safety in the total population, this would make asfotase alfa a product several times the value of Strensiq.
Speaker #11: If so, I may say that this is these programs—1,850 of covers—so that we would know the question we've been asking a lot about Strensiq, and answer to that now: we are expecting results in the first half of 2026.
Speaker #11: we'll we are this put all And together hopefully we'll in the able to product for a submit is that pediatric be the much easier enzyme therapy .
Speaker #11: But much, another easier to utilize than—which has Strensiq—to be administered every day, every other day, of course, is, or, which of very, this cumbersome.
Speaker #11: provided product would once on every It other week . would provide a So great benefit . demonstrate And if we the efficacy total population safety in make would as alpha a product , this several times value of the scientific .
James Gordon: Thank you. It's Michael Leuchten from Jefferies. I think this is for Dave and Susan. TROPION-Lung07 now has QCS in the protocol. Is that also the plan for TROPION-Lung08? And can you talk about the relative importance of AVANZAR versus TL07, TL08?
Michael Leuchten: Thank you. It's Michael Leuchten from Jefferies. I think this is for Dave and Susan. TROPION-Lung07 now has QCS in the protocol. Is that also the plan for TROPION-Lung08? And can you talk about the relative importance of AVANZAR versus TL07, TL08?
Speaker #12: Thank you . Mike Luton from from I think for this is Jefferies . Dave and Susan and oh seven now qrx has in the protocol .
Speaker #12: Also, is that for about eight, and can you talk the plan or the importance of Avanza versus TLR7? TLR8.
[Company Representative] (AstraZeneca): Do you want me to go first? Okay. Thanks for the question. So TROPION-Lung08 is only in the PD-L1 greater than 50% trial characteristics. It makes sense for the biomarker to be applied within the TROPION-Lung07 population. And that's what the priority has been there, very similar to what we've seen with the AVANZAR redesign where we put it in the ITT but also in the biomarker-positive patient population. Obviously, between AVANZAR and TROPION-Lung07, we'll be answering the question about the added benefit of platinum in addition as well. And I think these are all important trials that have the opportunity to really position Dato-DXd as a key component of the first-line setting across multiple segments of that patient population.
Susan Galbraith: Do you want me to go first? Okay. Thanks for the question. So TROPION-Lung08 is only in the PD-L1 greater than 50% trial characteristics. It makes sense for the biomarker to be applied within the TROPION-Lung07 population. And that's what the priority has been there, very similar to what we've seen with the AVANZAR redesign where we put it in the ITT but also in the biomarker-positive patient population. Obviously, between AVANZAR and TROPION-Lung07, we'll be answering the question about the added benefit of platinum in addition as well. And I think these are all important trials that have the opportunity to really position Dato-DXd as a key component of the first-line setting across multiple segments of that patient population.
Speaker #3: Okay, first? Shall we go to the question? So, and longer is only in the PD-L1, you know, wait, greater than 50%. Than—thanks for the trial. It makes sense, characteristics.
Speaker #3: biomarker to the applied be within for the Tlr7 population . And priority that's what's they're very to what we've similar with the Avanza redesign , where we put the it at but also ITT , in the biomarker in the positive patient population .
Speaker #3: seen Obviously , Avanza and Tlr7 will be answering the between the about question added benefit of . In platinum as of addition , you know , think these and I you know , all important trials that have the opportunity to really are , Dashaway position key as a component first line setting of the of that across multiple population segments
Pascal Soriot: Who has the microphone? Yeah. Go ahead.
Pascal Soriot: Who has the microphone? Yeah. Go ahead.
James Gordon: Thanks. Graham Parry from Citi. So it's another question following to Richard's question on camizestrant in the adjuvant setting. So CAMBRIA-1 is looking at essentially a switch from aromatase inhibitors. But the giredestrant/lidERA study suggests that perhaps that market opportunity might be quite small over time if giredestrant becomes standard of care in naïve patients in the intermediate-risk setting. So is there any plans to run a lidERA-like study? Or would you be looking predominantly at the market opportunity here coming in the high-risk population in combination with Verzenio? Thanks.
Graham Parry: Thanks. Graham Parry from Citi. So it's another question following to Richard's question on camizestrant in the adjuvant setting. So CAMBRIA-1 is looking at essentially a switch from aromatase inhibitors. But the giredestrant/lidERA study suggests that perhaps that market opportunity might be quite small over time if giredestrant becomes standard of care in naïve patients in the intermediate-risk setting. So is there any plans to run a lidERA-like study? Or would you be looking predominantly at the market opportunity here coming in the high-risk population in combination with Verzenio? Thanks.
Speaker #4: hasn't ? Yeah .
Speaker #10: Graham . Thanks ,
Speaker #10: It's another question, a question on the adjuvant setting. So, Cambria One is looking essentially at a switch from aromatase inhibitors.
Speaker #10: But the study . Giredestrant
Speaker #10: Suggests that that opportunity, who might be quite small, perhaps over market Giredestrant time. If standard of naive becomes care in patients in intermediate risk, is there any plans setting.
Speaker #10: To run a LADERA-like study, would you be looking predominantly at the market opportunity here, given the high risk in the SO population in combination with—thanks.
[Company Representative] (AstraZeneca): So just to go over again, the CAMBRIA-2 study is in a setting that's very similar to lidERA, but it does allow for the combination with abemaciclib, which I think is going to become an increasing piece. So of course, what lidERA doesn't answer is the relevance of the oral SERD in that context. And given that we think that CDK4/6 prevalence in the adjuvant setting is going to grow, I think it's very important to have the data with and without that combination and after a period of CDK4/6. That's why I'm saying when you look at the two trials in totality, I think it gives us the opportunity to have the greatest segment of the patient population, the adjuvant, should they both be positive. I don't know, Dave, do you want to comment?
Susan Galbraith: So just to go over again, the CAMBRIA-2 study is in a setting that's very similar to lidERA, but it does allow for the combination with abemaciclib, which I think is going to become an increasing piece. So of course, what lidERA doesn't answer is the relevance of the oral SERD in that context. And given that we think that CDK4/6 prevalence in the adjuvant setting is going to grow, I think it's very important to have the data with and without that combination and after a period of CDK4/6. That's why I'm saying when you look at the two trials in totality, I think it gives us the opportunity to have the greatest segment of the patient population, the adjuvant, should they both be positive. I don't know, Dave, do you want to comment?
Speaker #10: Vizinho ?
Speaker #3: just to So two studies in a setting that's very similar to Ladera , but it allow for the does combination with the Abemaciclib , is going to which I think an increasing piece .
Speaker #3: become So of Ladera doesn't what answer course , is the relevance of the oral serd in that And given context . that we think that Cdk4 six prevalence the adjuvant setting is grow , going to in in it's very the data with and without that important to have combination .
Speaker #3: a Cdk4 period of And after why I'm six . saying when That's you look at the two in in in totality , trials us the it gives I think opportunity to the have segment greatest patient the of population in the adjuvant .
Dave Fredrickson: Yeah. I'd simply amplify and echo some of the things that you had said previously, Susan, on this, which is if you think about Cambria I, which is in this 2 to 5-year population, that's the prevalent population. And so while it's true that over time, the upfront Cambria II population, we would expect to grow, there is a large population of patients that are prevalent on AI and AI-CDK4/6. And the program allows for looking at both AI and CDK4/6 combinations. It's the broadest program that also allows both that prevalent and incident pool. And it allows us to be in a competitive set of timelines by putting it together in the way that we have.
Dave Fredrickson: Yeah. I'd simply amplify and echo some of the things that you had said previously, Susan, on this, which is if you think about Cambria I, which is in this 2 to 5-year population, that's the prevalent population. And so while it's true that over time, the upfront Cambria II population, we would expect to grow, there is a large population of patients that are prevalent on AI and AI-CDK4/6. And the program allows for looking at both AI and CDK4/6 combinations. It's the broadest program that also allows both that prevalent and incident pool. And it allows us to be in a competitive set of timelines by putting it together in the way that we have.
Speaker #3: Should they be positive? I don't know if both will be, comment.
Speaker #2: Yeah . I simply amplify and echo things that you had said some of the previously . Susan , on is you think one , this , which is in about that's the Cambria , population .
Speaker #2: prevalent And so it's true that over which while upfront Cambria would two population , we , there time , the is a large expect population of to grow patients prevalent on AI that are and AI , Cdk4 six and the program looking allows for at both AI and Cdk4 six combinations .
Speaker #2: It's the broadest that also allows both that prevalent and incident competitive set of timelines together in pool, and it—
Pascal Soriot: Thanks, Dave. Can we go here and then maybe there?
Pascal Soriot: Thanks, Dave. Can we go here and then maybe there?
Simon Baker: Thanks, Pascal. Simon Baker from Rothschild & Co., Redburn. One, if I may, please, probably for Sharon. Could you just remind us of the points of differentiation of Tozorakimab, both in terms of the molecule and trial design, and how that underpins your confidence in the program? Thanks so much.
Simon Baker: Thanks, Pascal. Simon Baker from Rothschild & Co., Redburn. One, if I may, please, probably for Sharon. Could you just remind us of the points of differentiation of Tozorakimab, both in terms of the molecule and trial design, and how that underpins your confidence in the program? Thanks so much.
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Speaker #10: Sharon . Probably remind us of points one , if I of differentiation of the tocilizumab , both in terms of the way that the Dave .
Sharon Barr: Sure. And thanks for the question. So the story about Tozorakimab is the same one that we've been telling all along, which is that we think we have a highly differentiated IL-33 biologic. And the reason we think it's differentiated is because our molecule is able to hit both the ST2 pathway as well as the RAGE EGFR pathway and, importantly, to impact signaling downstream of that. And why does that matter? Because being able to inhibit signaling through RAGE EGFR is impacting mucus production and epithelial remodeling. And that's incredibly important in COPD where mucus production drives exacerbations. Exacerbations drive mucus production, and it gives you a vicious cycle. So we think that's a really important component to our IL-33. Now, as you know, we've designed a broad study to allow us to examine the efficacy of Tozorakimab in current and former smokers.
Sharon Barr: Sure. And thanks for the question. So the story about Tozorakimab is the same one that we've been telling all along, which is that we think we have a highly differentiated IL-33 biologic. And the reason we think it's differentiated is because our molecule is able to hit both the ST2 pathway as well as the RAGE EGFR pathway and, importantly, to impact signaling downstream of that. And why does that matter? Because being able to inhibit signaling through RAGE EGFR is impacting mucus production and epithelial remodeling. And that's incredibly important in COPD where mucus production drives exacerbations. Exacerbations drive mucus production, and it gives you a vicious cycle. So we think that's a really important component to our IL-33. Now, as you know, we've designed a broad study to allow us to examine the efficacy of Tozorakimab in current and former smokers.
Speaker #10: Trial design and how that underpins confidence in your program. Thanks so much, Sharon. Maybe...
Speaker #5: Thanks for the question. So, the go Tazorac about story one that we've been along, telling all that we which is have a highly, think we, differentiated IL-33 biologic.
Speaker #5: And the reason we think it's differentiated is because our molecule is able to hit both the ST2 pathway as well as the EGFR pathway, and
Speaker #5: Impact signaling—that downstream of that. And why does... Could you just—because it matters? Being able to inhibit signaling through RAGE, EGFR, is impacting mucus production, and that's incredibly important for remodeling.
Speaker #5: in epithelial COPD , where production drives mucus exacerbations drive mucus , exacerbations , production . And a vicious cycle . So we it gives you really component to IL 33 .
Speaker #5: know we've designed Now as you a broad study to examine the to efficacy of allow us tocilizumab in current and smokers . Our primary readout is in former smokers .
Sharon Barr: Our primary readout is in smokers, but we're looking at a broad population across eosinophil levels and across smoking status so that we have the opportunity to bring this to the broadest possible patient population.
Sharon Barr: Our primary readout is in smokers, but we're looking at a broad population across eosinophil levels and across smoking status so that we have the opportunity to bring this to the broadest possible patient population.
Speaker #5: We're looking at a broad population, but across eosinophil levels, smoking status, across—so that we have the opportunity to bring this to the possible patient population, have the broadest. And.
Pascal Soriot: Can we take one more question in the room? And then we'll take Steve Scala's question online.
Pascal Soriot: Can we take one more question in the room? And then we'll take Steve Scala's question online.
Iskra Reic: Yeah. Thanks. Christopher Uhde from.
Christopher Uhde: Yeah. Thanks. Christopher Uhde from.
Pascal Soriot: Do we can get a microphone over there? Yeah. Go ahead.
Pascal Soriot: Do we can get a microphone over there? Yeah. Go ahead.
Speaker #4: Every time . One more
Speaker #4: question in the room , and then we'll take . Steve question online . scholars Thanks , Yeah . Chris . Can we get a over microphone that ?
Christopher Uhde: Christopher Uhde from SEB. Thanks for taking my question. It's on Calquence and the room for growth. It's done a nice job beating again lately. Consensus has about 10%, give or take, growth for 2026 over 2025, then another 10% from then to about 2031, so peaks $4.4 billion. So will Amplify live up to its name, or is consensus in the right ballpark is my question? And are there any other meaningful gating events to unlock?
Christopher Uhde: Christopher Uhde from SEB. Thanks for taking my question. It's on Calquence and the room for growth. It's done a nice job beating again lately. Consensus has about 10%, give or take, growth for 2026 over 2025, then another 10% from then to about 2031, so peaks $4.4 billion. So will Amplify live up to its name, or is consensus in the right ballpark is my question? And are there any other meaningful gating events to unlock?
Speaker #4: . Chris , Yeah . Go ahead from Seb , thanks for question taking my . It's on for Calquence growth . in the room nice job beating done a again It's lately .
Speaker #4: Consensus has about taken for 10%, give or take. Then over 2025, 2026, another from 10%, then to about 2031. So, peaks at $4.4 billion.
Speaker #4: So amplify live name . Or is consensus in my its there up to we'll Is any ballpark ? events to the right And are unlock question .
Dave Fredrickson: So thanks, Chris, for the question. Amplify is very much an important part of the growth moving forward for Calquence, and the fact that we've got positive study approval within Europe, and we're anticipating the US approval is important. In general, the desire that we're hearing among hematologists across the multiple malignancies that they treat is to move towards more finite-based therapies. That trend has already happened within Europe. We've got, I think, a very differentiated and strong profile to be able to compete against the existing venetoclax-based options that are available there. In the US, remember that there is not a BCL2 and a BTKI combination finite CLL approach that's been approved. So we have an opportunity in the US to really be the first to come into this space. One in two patients are receiving finite as opposed to treat progression in the US.
Dave Fredrickson: So thanks, Chris, for the question. Amplify is very much an important part of the growth moving forward for Calquence, and the fact that we've got positive study approval within Europe, and we're anticipating the US approval is important. In general, the desire that we're hearing among hematologists across the multiple malignancies that they treat is to move towards more finite-based therapies. That trend has already happened within Europe. We've got, I think, a very differentiated and strong profile to be able to compete against the existing venetoclax-based options that are available there. In the US, remember that there is not a BCL2 and a BTKI combination finite CLL approach that's been approved. So we have an opportunity in the US to really be the first to come into this space. One in two patients are receiving finite as opposed to treat progression in the US.
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Speaker #2: very an much of important the growth . Moving part meaningful . Amplify And the forward got positive study approval within Europe and fact that we're anticipating the US approval is important in the general , desire that question hearing hematologists across the they malignancies that treat is to towards more move multiple based .
Speaker #2: Among what happened in finite Europe, and within that, I think we've got a very strong profile and are able to compete in a differentiated way against the existing Venetoclax-based options.
Speaker #2: Among what happened in Europe and within that finite group, I think we've got a very strong profile and are able to compete, differentiated against the existing Venetoclax-based options that are available. Remember, there is not a US option in this.
Speaker #2: BCL2—there's that, BTK, and a finite CLL approved. So that's been the approach, and we have an opportunity in this space too.
Speaker #2: BCL2 is there, BTK and a finite CLL approved. So that's been the approach—we have an opportunity in this space to really be first in the US to come into it. One in two patients are receiving it as a finite treatment to progression.
Dave Fredrickson: So you can see how getting to growth numbers within the US, which is certainly the largest portion of our global Calquence sales, really can be very, very meaningful. The other places, in terms of opportunities, we have continued opportunity to expand ECHO in the second-line MCL. And we also have DLBCL with Escalade, which is something that'll read out a little bit later on.
Dave Fredrickson: So you can see how getting to growth numbers within the US, which is certainly the largest portion of our global Calquence sales, really can be very, very meaningful. The other places, in terms of opportunities, we have continued opportunity to expand ECHO in the second-line MCL. And we also have DLBCL with Escalade, which is something that'll read out a little bit later on.
Speaker #2: In the . So you can US see getting to growth opposed to within the US , which is certainly the largest our global portion of calquence sales , really can be very , very meaningful .
Speaker #2: other The places , in terms of we have opportunities , continued to expand opportunity echo . And the second line , MCL . And we also DLBCL have Escalade , which something that I'll read a is little bit later on out .
Pascal Soriot: Go ahead. We need a microphone there. Yeah. Go.
Pascal Soriot: Go ahead. We need a microphone there. Yeah. Go.
Simon Baker: Okay. Yeah. It's Justin Smith from Bernstein. Sharon, one for you, if that's okay. CardioTransform. Could you just remind us on the powering with regards to monotherapy versus combo with TAF? Is the TAF combo arm big enough to prove something clinically meaningful?
Justin Smith: Okay. Yeah. It's Justin Smith from Bernstein. Sharon, one for you, if that's okay. CardioTransform. Could you just remind us on the powering with regards to monotherapy versus combo with TAF? Is the TAF combo arm big enough to prove something clinically meaningful?
Speaker #10: Okay .
Speaker #4: Yeah. We need a microphone.
Speaker #10: Okay. Yeah. It's Smith from
Speaker #10: One for you, if that's okay. Cardio.
Speaker #10: Remind us, you just — Bernstein. Powering with regards to monotherapy on the ON versus combo GO transforms TAF with combo TAF. Is enough, clinically, the something meaningful? Arm big — how?
Sharon Barr: Right. So this question comes up a lot with Wainua. And I think it really speaks to the interest in novel therapeutics for patients living with ATTR-CM, which is a growing patient population as diagnostic rates improve. Now, we have designed, as I mentioned earlier today, the largest-ever cardiomyopathy study so that we would be powered to do preplanned subgroup analyses. One of those is to be able to differentiate between patients on baseline tafamidis versus those who are not. And our trial will have the largest proportion and number of patients who are on baseline tafamidis. So should we be able to proceed through the statistical hierarchy and answer that question, we have designed a trial that allows us specifically to get at that.
Sharon Barr: Right. So this question comes up a lot with Wainua. And I think it really speaks to the interest in novel therapeutics for patients living with ATTR-CM, which is a growing patient population as diagnostic rates improve. Now, we have designed, as I mentioned earlier today, the largest-ever cardiomyopathy study so that we would be powered to do preplanned subgroup analyses. One of those is to be able to differentiate between patients on baseline tafamidis versus those who are not. And our trial will have the largest proportion and number of patients who are on baseline tafamidis. So should we be able to proceed through the statistical hierarchy and answer that question, we have designed a trial that allows us specifically to get at that.
Speaker #5: So, I think really this question comes up.
Speaker #5: with Wainua . cardiomyopathy , which And I interest in is a growing the improve . diagnostic therapeutics for Now a lot population . designed , earlier today , as I the study , cardiomyopathy ever so that we would be we have right . largest analyses .
Speaker #5: With Wainua, cardiomyopathy, which—and I think what is interesting—is a growing area to improve diagnostics and therapeutics for. Now, a lot of the population is being designed, and earlier today, as I mentioned, the study on cardiomyopathy ever—so that we would be where we are right now.
Speaker #5: With Wainua, cardiomyopathy—which I am interested in—is a growing area with opportunities to improve diagnostics and therapeutics. Now, a lot of the population is being diagnosed earlier. Today, as I mentioned, the study is one of the largest preplanned subgroup trials for cardiomyopathy that we have right now. And our aim is to be able to identify those in the trial.
Speaker #5: Proportion in, of number on baseline, the—should we be able to proceed through the statistical hierarchy—answer that, and largest is to be. We have designed a Tafamidis.
Sharon Barr: And we think it's important because that's going to inform treatment guidelines for patients and help to shape the way cardiomyopathy patients are treated in the clinic. So we look forward to the readout of this in the second half of this year. And we'll share the data when they are mature.
Sharon Barr: And we think it's important because that's going to inform treatment guidelines for patients and help to shape the way cardiomyopathy patients are treated in the clinic. So we look forward to the readout of this in the second half of this year. And we'll share the data when they are mature.
Speaker #5: Specifically to that, and we question: who are on think it's treatment guidelines for get at and help to the way patients shape, are patients cardiomyopathy important because clinic.
Pascal Soriot: Thanks, Sharon. So we'll take Steve Scala's question online and then return to the room. I think Rajan has the microphone. So Steve, over to you.
Pascal Soriot: Thanks, Sharon. So we'll take Steve Scala's question online and then return to the room. I think Rajan has the microphone. So Steve, over to you.
Speaker #5: So we forward to the, in the readout, in the look allows mature the data we'll share year, and.
Dave Fredrickson: Thank you, Pascal. A general question, but a hellaciously competitive market of undifferentiated products, which isn't growing very much despite huge awareness, doesn't strike me as the type of market AstraZeneca pursues aggressively. Obesity could be described as that. And you are not only involved but increased exposure. So what am I missing? Are you assuming that fundamentals improve, that pricing stabilizes and increases, that strong growth will resume? I know that you're pursuing combos, but value-added products launched into a tough market would strike me as a high-probability path to success. And if I could just tack on, can you shed light on why AstraZeneca continues to pursue an oral relaxant? Thank you.
[Analyst]: Thank you, Pascal. A general question, but a hellaciously competitive market of undifferentiated products, which isn't growing very much despite huge awareness, doesn't strike me as the type of market AstraZeneca pursues aggressively. Obesity could be described as that. And you are not only involved but increased exposure. So what am I missing? Are you assuming that fundamentals improve, that pricing stabilizes and increases, that strong growth will resume? I know that you're pursuing combos, but value-added products launched into a tough market would strike me as a high-probability path to success. And if I could just tack on, can you shed light on why AstraZeneca continues to pursue an oral relaxant? Thank you.
Speaker #4: Thanks, John. Scholars, take return to the Rajan. Steve, over to you. Room. So
Speaker #4: Thanks, John. Scholars, take return to the Rajan. Steve, over to you. Room.
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Iskra Reic: Yeah. So no, I think it's a fair question. First of all, I think we truly believe that the market in itself is still quite immature. Yes, injectables have their place. The first orals are moving in. But there's still so much improvement possible. And combination therapies for obesity, overweight people, I think are very crucial in order to help those patients to reduce their risk of cardiovascular events. So that's one big ticket item. Second part is that those products are still not very much used in, let's say, the international markets. If you look at the success of Farxiga, a big part of the success of Farxiga across the three indications is that we have a very large footprint in the international markets. So there's clearly room to maneuver.
Ruud Dobber: Yeah. So no, I think it's a fair question. First of all, I think we truly believe that the market in itself is still quite immature. Yes, injectables have their place. The first orals are moving in. But there's still so much improvement possible. And combination therapies for obesity, overweight people, I think are very crucial in order to help those patients to reduce their risk of cardiovascular events. So that's one big ticket item. Second part is that those products are still not very much used in, let's say, the international markets. If you look at the success of Farxiga, a big part of the success of Farxiga across the three indications is that we have a very large footprint in the international markets. So there's clearly room to maneuver.
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Iskra Reic: The third piece is that we are doing a lot of research and development work regarding the quality of weight loss. Yes, it's not only about the percentage of weight loss, but also, are you able to preserve lean muscle, yes or no? Are you able to attach or attack the bad fat, the visceral fat? So I think there are still an enormous amount of possibilities to move to the next generation of anti-obese medicines. And I truly believe that AstraZeneca is one of those companies well-equipped in order to address those questions. I think we have an excellent development and discovery team. You have seen our excitement of the deal we made last week with CSPC, which gives an opportunity to move in long-acting medicines. So I think there's still so much to win in this marketplace. And we're keen to play an important role in that.
Ruud Dobber: The third piece is that we are doing a lot of research and development work regarding the quality of weight loss. Yes, it's not only about the percentage of weight loss, but also, are you able to preserve lean muscle, yes or no? Are you able to attach or attack the bad fat, the visceral fat? So I think there are still an enormous amount of possibilities to move to the next generation of anti-obese medicines. And I truly believe that AstraZeneca is one of those companies well-equipped in order to address those questions. I think we have an excellent development and discovery team. You have seen our excitement of the deal we made last week with CSPC, which gives an opportunity to move in long-acting medicines. So I think there's still so much to win in this marketplace. And we're keen to play an important role in that.
Speaker #8: we have is that there's success of international third piece we say , the are doing a research footprint development work success quality one big weight loss The the only about the percentage of weight loss , improvement It's not but markets the not preserve able of of of no ?
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Speaker #8: So
Speaker #8: I, of course, am equipped in order to answer your questions regarding this. I have used and have seen much of the data from last week, which gives us an opportunity to maneuver and move in the market.
Speaker #8: excitement
Speaker #8: medicines . So I possibilities to The so there's move to the win in excellent marketplace our play an visceral to are keen to fat ?
Pascal Soriot: Thank you, Owen.
Pascal Soriot: Thank you, Owen.
James Gordon: Thanks for taking my question. It's Rajan Sharma from Goldman Sachs. I just wanted to focus on the growth drivers in 2026 outside of oncology. Do you think the biopharma business can grow through the Farxiga LOE? And then just thinking about the guidance 2026 at the group level, what has to go right to get to the upper end of that guidance? And when do we get visibility on those factors?
Rajan Sharma: Thanks for taking my question. It's Rajan Sharma from Goldman Sachs. I just wanted to focus on the growth drivers in 2026 outside of oncology. Do you think the biopharma business can grow through the Farxiga LOE? And then just thinking about the guidance 2026 at the group level, what has to go right to get to the upper end of that guidance? And when do we get visibility on those factors?
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Iskra Reic: Yeah. So let me take that question as a start. First of all, I think the respiratory and immunology portfolio is growing very fast. It was already $9 billion in the course of 2025. There's no reason to believe that products like Breztri, potentially also with asthma, what I said in my prepared remarks, products like Tezspire, Fasenra, are not growing anymore, double-digit, moving forward. So that is, I think, a very important growth driver, not only in the United States and Europe, but also clearly in the international markets. So that's one big ticket item. The other one is clearly that, hopefully, we will see the approval of Baxdrostat in the course of this year as an approval. Now, that, of course, will not immediately generate substantial sales in the course of 2026. It's a highly dominated Part D population.
Ruud Dobber: Yeah. So let me take that question as a start. First of all, I think the respiratory and immunology portfolio is growing very fast. It was already $9 billion in the course of 2025. There's no reason to believe that products like Breztri, potentially also with asthma, what I said in my prepared remarks, products like Tezspire, Fasenra, are not growing anymore, double-digit, moving forward. So that is, I think, a very important growth driver, not only in the United States and Europe, but also clearly in the international markets. So that's one big ticket item. The other one is clearly that, hopefully, we will see the approval of Baxdrostat in the course of this year as an approval. Now, that, of course, will not immediately generate substantial sales in the course of 2026. It's a highly dominated Part D population.
Speaker #6: And visibility on the upper, we get.
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Speaker #6: About the level, oncology, do you—
Speaker #6: About the level, oncology—do you mean those, Farxiga and, yeah.
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Speaker #8: I said in Bayer 2025 . Fasenra growing anymore . prepared are not forward . . that is , probably like important growth not only in United States the team .
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Speaker #8: international moving one one big ticket item . and Europe , course a very clearly that digit we will see I think , the or First remarks , Baxter and reason that's course of stat in the .
Speaker #8: approval That of The when do sales approval of substantial It's dominated D , but based on all the market of truly population believe that this product has research , we in the course a course will markets .
Iskra Reic: But based on all the market research, we truly believe that this product has a multi-billion-dollar opportunity as well. So if you see our internal forecast, yes, we will have a blip for sure regarding the Farxiga LOE. But there are enough other growth drivers in order to compensate and potentially to exceed the growth moving forward. So we are quite bullish in our internal forecast regarding the forecast for the biopharma business.
Ruud Dobber: But based on all the market research, we truly believe that this product has a multi-billion-dollar opportunity as well. So if you see our internal forecast, yes, we will have a blip for sure regarding the Farxiga LOE. But there are enough other growth drivers in order to compensate and potentially to exceed the growth moving forward. So we are quite bullish in our internal forecast regarding the forecast for the biopharma business.
Speaker #8: compensate and exceed the business. And so,
[Analyst] (ATPP): Hi. Rajesh Kumar from ATPP. Looking at 2026, you're sitting at 1.2 times net debt to EBITDA. You've got consensus, which is inching by the minute close to your $80 billion target by 2030. You've got a few patent cliffs soon after that. When you think of capital allocation, people have factored in a higher R&D in their models now. Would you go the organic route to basically support growth beyond 2030, or what sort of firepower do you intend to deploy for acquisitions? The question is basically underpinned by what Steve Scala was asking earlier, that you've gone to obesity at a time where almost no one is sure whether this market has the same kind of growth. And every player is going in. So if you keep going organically into different segments, you might run out of ideas.
[Analyst] (ATPP): Hi. Rajesh Kumar from ATPP. Looking at 2026, you're sitting at 1.2 times net debt to EBITDA. You've got consensus, which is inching by the minute close to your $80 billion target by 2030. You've got a few patent cliffs soon after that. When you think of capital allocation, people have factored in a higher R&D in their models now. Would you go the organic route to basically support growth beyond 2030, or what sort of firepower do you intend to deploy for acquisitions? The question is basically underpinned by what Steve Scala was asking earlier, that you've gone to obesity at a time where almost no one is sure whether this market has the same kind of growth. And every player is going in. So if you keep going organically into different segments, you might run out of ideas.
Speaker #4: Hi
Speaker #4: .
Speaker #14: Rajesh
Speaker #14: Rajesh
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Speaker #14: net debt to Kumar EBITDA . You regarding forecast , we will 1.2 times you're sitting
Speaker #14: consensus , minute close to your $80 billion target
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Speaker #14: . think dollar capital people allocation , factored in a higher R&D in their models . Now opportunity as for . When you go the organic route basically , you know , support growth .
Speaker #14: 2030 or , you beyond of what sort firepower do you intend to for know , acquisitions ? The question is underpinned deploy Scala earlier that obesity to where time Would almost no one is sure basically this , what you know , market has the same kind of was whether , and asking every player is going growth if you in .
[Analyst] (ATPP): So how are you thinking about that problem in terms of reallocation of capital, share buyback, or future investments?
[Analyst] (ATPP): So how are you thinking about that problem in terms of reallocation of capital, share buyback, or future investments?
Speaker #14: So organically into segments different , you run , run out of ideas . So about that problem you you've gone terms in reallocation of thinking buyback capital , share investments .
Pascal Soriot: So let me make a general comment. Then Aradhana can make more specific comments about capital allocation. One thing I would add to what Ruud said about our GLP-1 and others is cardiometabolic is going to be, is today, the biggest issue mankind is facing. And we are in the early phase of this transformation and the way we can actually tackle this disease, if you want. And beyond our GLP-1, you also have SGLT2. And I really believe in the oral segment. Combining those two, it's going to make a huge difference to how people are treated. I think the foundation treatment of many of these people should be our GLP-1 and then SGLT2, protect the kidneys, the heart, reduce weight, improve metabolic status. And then beyond that, we have other mechanisms, of course. So I think this is going to remain. I mean, it is looking very crowded.
Pascal Soriot: So let me make a general comment. Then Aradhana can make more specific comments about capital allocation. One thing I would add to what Ruud said about our GLP-1 and others is cardiometabolic is going to be, is today, the biggest issue mankind is facing. And we are in the early phase of this transformation and the way we can actually tackle this disease, if you want. And beyond our GLP-1, you also have SGLT2. And I really believe in the oral segment. Combining those two, it's going to make a huge difference to how people are treated. I think the foundation treatment of many of these people should be our GLP-1 and then SGLT2, protect the kidneys, the heart, reduce weight, improve metabolic status. And then beyond that, we have other mechanisms, of course. So I think this is going to remain. I mean, it is looking very crowded.
Speaker #4: So let me make a general
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Speaker #4: treated . I think the , future foundation treatment of many of these people GLP one . be others protect the Sglt2 kidneys , the heart , should weight , reduce improve metabolic status to And beyond that , we have then , other is going to I mean , it is looking crowded , is also a issue this huge for over time , I And settle down think because not succeed in this everybody will , and medicine .
Pascal Soriot: But it is also a huge issue for medicine. And over time, I think things will settle down because not everybody will succeed in this market. We have the pipeline. We have our industry strengths and particular development strengths. And we have the commercial network and the manufacturing network to manufacture those products and commercialize them around the world. So I think it will continue to it will be an important issue to tackle from a medical viewpoint. And it will be a driving growth for us, a driver of growth. And we'll become profitable as soon as we can get to scale. In terms of a general question about capital allocation?
Pascal Soriot: But it is also a huge issue for medicine. And over time, I think things will settle down because not everybody will succeed in this market. We have the pipeline. We have our industry strengths and particular development strengths. And we have the commercial network and the manufacturing network to manufacture those products and commercialize them around the world. So I think it will continue to it will be an important issue to tackle from a medical viewpoint. And it will be a driving growth for us, a driver of growth. And we'll become profitable as soon as we can get to scale. In terms of a general question about capital allocation?
Speaker #4: the have strengths , and commercial pipeline , we we have the network and the market network to strengths and manufacture those products manufacturing remain and think it will around the world .
Speaker #4: Continue to commercialize them, so I think it will be an issue to tackle from an R&D medical viewpoint, and it will be a driver of growth and will help us.
Aradhana Sarin: Yeah. So a few things to clarify. So the $80 billion ambition was on an organic basis. And that does not assume any M&A of any size and scale. And I think we're on track to achieve that. We do have substantial firepower. I think we're very comfortable at 1.2x leverage. But we have plenty of capacity. That being said, I think we remain very disciplined in terms of what type of assets we bring in because it's not about just buying assets. It's about actually creating value for shareholders from those assets that we acquire. And that requires substantial investments in R&D once we acquire those assets or license those assets, etc. And so again, we are very disciplined in how we do that. And we need to continue to add value.
Aradhana Sarin: Yeah. So a few things to clarify. So the $80 billion ambition was on an organic basis. And that does not assume any M&A of any size and scale. And I think we're on track to achieve that. We do have substantial firepower. I think we're very comfortable at 1.2x leverage. But we have plenty of capacity. That being said, I think we remain very disciplined in terms of what type of assets we bring in because it's not about just buying assets. It's about actually creating value for shareholders from those assets that we acquire. And that requires substantial investments in R&D once we acquire those assets or license those assets, etc. And so again, we are very disciplined in how we do that. And we need to continue to add value.
Speaker #4: Profitable—get to as soon as important, yeah. Scale, in terms of general allocation.
Speaker #4: question about
Speaker #4: question about
Speaker #1: So
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Speaker #1: about assets that we shareholders acquire . requires , you know we creating assets about etc. . And so Once we , again , we or that are in how investments in we do that .
Aradhana Sarin: I think on your question of beyond 2030, that's why Pascal highlighted all. I mean, if you look at our R&D expense, a substantial portion of that, I wouldn't say the majority, but a substantial portion is going actually in assets which won't have any substantial revenue in 2030. So that's all the investment for the beyond 2030 to continue the growth rate because we know in that time frame, there are going to be substantial LOEs.
Aradhana Sarin: I think on your question of beyond 2030, that's why Pascal highlighted all. I mean, if you look at our R&D expense, a substantial portion of that, I wouldn't say the majority, but a substantial portion is going actually in assets which won't have any substantial revenue in 2030. So that's all the investment for the beyond 2030 to continue the growth rate because we know in that time frame, there are going to be substantial LOEs.
Speaker #1: know , the highlighted majority , but a all say , at our portion is actually in won't have any substantial revenue all the that's assets which going investment for 2030 to substantial growth I mean , rate , because continue the the that time frame there are going losses .
Speaker #1: 2030 .
Pascal Soriot: If you look at it, I mean, we are in a good position. We don't have to go after a phase where assets that are proven and cost a fortune and you pay a front, which you're going to get later. We really try to focus our busy activities on earlier assets where we can add value and create shareholder value because we don't need products immediately. We need to invest for the future. And so our strategy really has been to build our pipeline, of course, and add to it, but through earlier busy investments and then add value over time. So that's really our strategy. And as you said, we have a good capacity in terms of raising debt if we wanted to. But we also have to absorb all these products in our P&L, right? So it's not only a question of cash.
Pascal Soriot: If you look at it, I mean, we are in a good position. We don't have to go after a phase where assets that are proven and cost a fortune and you pay a front, which you're going to get later. We really try to focus our busy activities on earlier assets where we can add value and create shareholder value because we don't need products immediately. We need to invest for the future. And so our strategy really has been to build our pipeline, of course, and add to it, but through earlier busy investments and then add value over time. So that's really our strategy. And as you said, we have a good capacity in terms of raising debt if we wanted to. But we also have to absorb all these products in our P&L, right? So it's not only a question of cash.
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Speaker #4: a good don't have to go after phase three assets that are proven in position . fortune . And front , which you're going to
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Speaker #4: And strategy really has so our our pipeline . course . invest for And to it . Of build in through But add value over that's really our and then to And as investments you said , we we substantial have a good BD capacity in of raising debt .
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Speaker #4: earlier Scale people
Pascal Soriot: It's a question of P&L too and a question of focus. We have a very broad portfolio. But within this, we need to stay focused on what our key priorities are. Yeah.
Pascal Soriot: It's a question of P&L too and a question of focus. We have a very broad portfolio. But within this, we need to stay focused on what our key priorities are. Yeah.
Speaker #4: PNL . Right . So , but we it's not only a absorb in . question of cash , the all these focus PNL , too , and a question of a very broad .
[Company Representative] (AstraZeneca): There's one online.
[Company Representative] (AstraZeneca): There's one online.
Speaker #4: but within this we need to stay focused on what our key priorities are We have . Yeah .
Pascal Soriot: Oh, sorry. Online. Oh, that's what you mean. Oh, sorry. Peter at BNP. Over to you, Peter Verdult.
Pascal Soriot: Oh, sorry. Online. Oh, that's what you mean. Oh, sorry. Peter at BNP. Over to you, Peter Verdult.
Speaker #1: There's one online .
Speaker #4: Oh , sorry . Online . Oh , that's what you mean , Peter , at BNP . Over to you Peter . . So Adult .
Speaker #4: Oh , sorry . Online . Oh , that's what you mean , Peter , at BNP . Over to you Peter . . So Adult Sorry
Operator: Thanks, Pascal. Peter Verdult here from BNP. Sorry I can't be with you live. Just two quick ones, please. Susan and Sharon. For Susan on Alteogen, can we just have an update here in your confidence in this formulation technology significantly extending your key oncology biologic franchises? Are there any projects you can call out that will be leading the charge or entering the clinic in the next 12 months? Secondly, for Sharon, sorry to do it in person to death. But can I just try my luck? Can you sketch out in a little more detail what Astra would consider a win given existing SLE data in the market? But put simply, do you think you can raise the bar further on outcomes in the SLE market? Thank you.
[Analyst] (BNP): Thanks, Pascal. Peter Verdult here from BNP. Sorry I can't be with you live. Just two quick ones, please. Susan and Sharon. For Susan on Alteogen, can we just have an update here in your confidence in this formulation technology significantly extending your key oncology biologic franchises? Are there any projects you can call out that will be leading the charge or entering the clinic in the next 12 months? Secondly, for Sharon, sorry to do it in person to death. But can I just try my luck? Can you sketch out in a little more detail what Astra would consider a win given existing SLE data in the market? But put simply, do you think you can raise the bar further on outcomes in the SLE market? Thank you.
Speaker #15: from out here can't be with you . just two quick Live please . Susan and Sharon . for gin . Can we just Sorry , I update here BNP in this Technology Susan extending your key oncology biologic franchises .
Speaker #15: Are there any projects you can call on that will be the ones leading the charge or entering the clinic in the next 12 months?
Speaker #15: Are there any projects you can call on that will be ones , leading the in your charge or entering the clinic confidence Secondly , in the Sharon , sorry .
Speaker #15: And person significantly death , next for to luck ? Can but can I out in a detail to do consider a Astra would just sketch what you win data in the market ?
Pascal Soriot: Can we focus on the first question? If we have time, we will return to the second one later.
Pascal Soriot: Can we focus on the first question? If we have time, we will return to the second one later.
Speaker #15: existing think you
Speaker #15: That , formulation ? put can raise the bar given on outcomes in the Thank you .
[Company Representative] (AstraZeneca): Yeah. So obviously, I think subcutaneous formulations have the opportunity to offer convenience to patients, which I think is very attractive. We're obviously investing in this across our immuno-oncology portfolio, the bispecifics and the ADCs to look at. But also, we have the opportunity to look at subcutaneous formulations also with our ADC portfolio, which is perhaps slightly more surprising to people. But it is possible to do that in certain circumstances. And then, of course, across our T-cell engagers, the actual doses in the T-cell engager portfolio are often low enough that enables a subcutaneous formulation without necessarily requiring something like the hyaluronidase technology as well. So I would just say that this is a trend that you've seen already across multiple different settings and is one that I think will continue to grow across the biologic part of the portfolio.
Aradhana Sarin: Yeah. So obviously, I think subcutaneous formulations have the opportunity to offer convenience to patients, which I think is very attractive. We're obviously investing in this across our immuno-oncology portfolio, the bispecifics and the ADCs to look at. But also, we have the opportunity to look at subcutaneous formulations also with our ADC portfolio, which is perhaps slightly more surprising to people. But it is possible to do that in certain circumstances. And then, of course, across our T-cell engagers, the actual doses in the T-cell engager portfolio are often low enough that enables a subcutaneous formulation without necessarily requiring something like the hyaluronidase technology as well. So I would just say that this is a trend that you've seen already across multiple different settings and is one that I think will continue to grow across the biologic part of the portfolio.
Speaker #4: Can we focus on the first question and, to the return, second one? Yeah, we will.
Speaker #4: Can we focus on the first question and to the return second one
Speaker #3: obviously I think to offer convenience to to
Speaker #3: And attractive . we're obviously investing in across
Speaker #3: And attractive . we're obviously investing in across our immuno
Speaker #3: portfolio . The
Speaker #3: to to look at . But silence have the to , to look at opportunity formulations . subcutaneous Also with ADC our the portfolio formulations have little more , you oncology silencing market ?
Speaker #3: slightly more is possible people , but do that in certain And of circumstances . course , . T-cell And to engagers , Bispecifics this the engager the actual T-cell portfolio are often low is know , which the that that enough enables you know , also we formulation without necessarily something requiring hyaluronidase like as technology just say that I would a already trend that So well .
Pascal Soriot: And Sharon?
Pascal Soriot: And Sharon?
Operator: Sure. So going back to CardioTransform for Wainua, a few things to note about our clinical trial relative to competitors' clinical trial. The first is that the key objective of CardioTransform was to have a balance of naive patients and tafamidis patients. And given that CardioTransform is the largest ever trial run in this setting, we've achieved that. So we'll be able to address that question pending positive results, which we think will be very informative to the clinical community. And the second is that CardioTransform allows for stabilizer drop-ins, so tafamidis drop-ins, which speaks to the remaining unmet medical need. We know that patients who are currently on stabilizers continue to progress on therapy. If that were not true, we wouldn't be able to enroll our trial.
Sharon Barr: Sure. So going back to CardioTransform for Wainua, a few things to note about our clinical trial relative to competitors' clinical trial. The first is that the key objective of CardioTransform was to have a balance of naive patients and tafamidis patients. And given that CardioTransform is the largest ever trial run in this setting, we've achieved that. So we'll be able to address that question pending positive results, which we think will be very informative to the clinical community. And the second is that CardioTransform allows for stabilizer drop-ins, so tafamidis drop-ins, which speaks to the remaining unmet medical need. We know that patients who are currently on stabilizers continue to progress on therapy. If that were not true, we wouldn't be able to enroll our trial.
Speaker #3: across is to grow multiple across the biologics part of the portfolio.
Speaker #4: In and Chan .
Speaker #5: Sure . So going to Transform for a plantaricin
Speaker #5: few things to to note about our competitors , clinical The first is that back objective of Cardio Transform
Speaker #5: naive relative to the key trial . very given that cardio was to have largest ever trial this setting , achieved that . So we'll we've be able to address that this pending positive a results , which we balance of think will be very and informative to the clinical run in patients . community .
Speaker #5: naive relative to the key trial . very given that cardio was to have largest ever trial this setting , achieved that . So we'll we've be able to address that this pending positive a results , which we balance of think will be very and informative to the clinical run in patients .
Speaker #5: And the stabilizer drop ins . acoramidis drop ins , which speaks to the medical need . We know that patients who remaining currently on are stabilizers for on continue to true , we that were not So succeeding silencer on top of their of care , including therapy .
Operator: So understanding how those patients are succeeding on a silencer on top of their standard of care, including a stabilizer, is incredibly important. It's also important to note that in this larger trial, we have specific hard cardiac endpoints, including cardiovascular mortality as opposed to all-cause mortality, which really helps us understand how this drug is doing what it's doing and how it ultimately impacts those important readouts for patients who are living with ATTR cardiomyopathy. So overall, we expect to have landmark data for overall benefit and be able to demonstrate the additive benefit of a silencer on top of stabilizers.
Sharon Barr: So understanding how those patients are succeeding on a silencer on top of their standard of care, including a stabilizer, is incredibly important. It's also important to note that in this larger trial, we have specific hard cardiac endpoints, including cardiovascular mortality as opposed to all-cause mortality, which really helps us understand how this drug is doing what it's doing and how it ultimately impacts those important readouts for patients who are living with ATTR cardiomyopathy. So overall, we expect to have landmark data for overall benefit and be able to demonstrate the additive benefit of a silencer on top of stabilizers.
Speaker #5: readouts for patients who able to ATR So overall , we cardiomyopathy . to landmark data for overall and be able to have additive silencer on top of stabilizers the of a
Pascal Soriot: So maybe we take the last one. Mattias Häggblom at Handelsbanken is on the line over to you, Mattias. Yep. Yep.
Pascal Soriot: So maybe we take the last one. Mattias Häggblom at Handelsbanken is on the line over to you, Mattias. Yep. Yep.
Speaker #4: we
Speaker #4: take the . So maybe patients are Mathias last one . Benken is on Mathias the line . Over to you . Mathias .
[Company Representative] (AstraZeneca): I'm curious to hear how you think about AstraZeneca's competitive advantage from an in-licensing or M&A point of view, given you have two science sites in China when competing for assets with a competitor who does not have R&D on site in China.
[Company Representative] (AstraZeneca): I'm curious to hear how you think about AstraZeneca's competitive advantage from an in-licensing or M&A point of view, given you have two science sites in China when competing for assets with a competitor who does not have R&D on site in China.
Speaker #4: , please Yes
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Speaker #16: . I'm curious to AstraZeneca . Competitive about from an enlightening or hear how you M&A with view advantage rapidly Given point of sites .
Speaker #16: China for competing assets with a you have not have competitor who in does China on
Pascal Soriot: So the first part of your question was a bit hard to understand. But I think you're asking us about our position in China from a business viewpoint. If that's the question, let me try. And I'm absolutely convinced we need to be in China to collaborate with, partner with Chinese companies, but also to compete and learn to compete with them and how they compete, not only commercially but mostly from an R&D perspective because the world has changed. And they are increasingly becoming a fundamental part of innovation in our industry. And some of them, at some point, will become global companies. So it's fundamental for us to be there. And I think we have quite a good position to do this. We have two R&D centers. We have a strong position, strong profile in China.
Pascal Soriot: So the first part of your question was a bit hard to understand. But I think you're asking us about our position in China from a business viewpoint. If that's the question, let me try. And I'm absolutely convinced we need to be in China to collaborate with, partner with Chinese companies, but also to compete and learn to compete with them and how they compete, not only commercially but mostly from an R&D perspective because the world has changed. And they are increasingly becoming a fundamental part of innovation in our industry. And some of them, at some point, will become global companies. So it's fundamental for us to be there. And I think we have quite a good position to do this. We have two R&D centers. We have a strong position, strong profile in China.
Speaker #4: question was bit
Speaker #4: understand , but I So think you're asking us about position in China bit hard to from a point . If that's the let me try question , our the first part of , I'm convinced absolutely
Speaker #4: in you know collaborate and with companies , but also to compete and Chinese learn partner with compete and how with them compete . , learn to when commercially , but they from an R&D we need because the to be has and the are increasingly becoming a fundamental part of some of them at some point will become global .
Speaker #4: it's fundamental . So And I And be there . have think we quite a good position to do this . a strong position , strong profile changed have two R&D .
Pascal Soriot: A few of the deals we've made, we were able to make because people wanted to work with us. With the recent deal we made, I know that someone else wanted to pay more money. But the company wanted to work with us. So I think that relationship we build with local Chinese companies over time, and our reputation, and our focus, and the focus they know that we have on a few limited diseases have really helped us secure a number of deals over the last few years. Now, what happens, though, is the cost, the price, the price of these busy deals is going up, right? And I assume that would be the case. And that's why after COVID, and when the country reopened, we quickly went there. And we've done quite a number of deals over the last few years at reasonable prices.
Pascal Soriot: A few of the deals we've made, we were able to make because people wanted to work with us. With the recent deal we made, I know that someone else wanted to pay more money. But the company wanted to work with us. So I think that relationship we build with local Chinese companies over time, and our reputation, and our focus, and the focus they know that we have on a few limited diseases have really helped us secure a number of deals over the last few years. Now, what happens, though, is the cost, the price, the price of these busy deals is going up, right? And I assume that would be the case. And that's why after COVID, and when the country reopened, we quickly went there. And we've done quite a number of deals over the last few years at reasonable prices.
Speaker #4: A of the deals we've made , we were for us to make because able to people wanted to work with And not . We've , in you know , the few recent deal we We made .
Speaker #4: I know that wanted to pay more money , but wanted to that innovation in our relationship we centers . someone us local Chinese companies time , and think now the and reputation build over focus and the with else have on our limited diseases really helped us have of deals company last few years .
Speaker #4: secure over the what is the cost . The the bid , is going a few up BD digital focus , they right happens , though , this ?
Speaker #4: that's price , I assume that's why Covid after and case . the And country reopened , we there and we've that we quite that would a number of know last few over the reasonable is more difficult because quickly went everybody is going price of .
Pascal Soriot: And it's becoming more difficult because everybody's going there. But yes, I continue to think we have a good position. We can leverage our position in China. But we will have to remain disciplined because there's competition for deals. And the prices are going up. And of course, we have to stay focused on what we're doing. So Andy, I think we have to stop here. Some of us have to be on the roadshow. So thank you so much for all your interest, and your great questions. Have a good rest of the day.
Pascal Soriot: And it's becoming more difficult because everybody's going there. But yes, I continue to think we have a good position. We can leverage our position in China. But we will have to remain disciplined because there's competition for deals. And the prices are going up. And of course, we have to stay focused on what we're doing. So Andy, I think we have to stop here. Some of us have to be on the roadshow. So thank you so much for all your interest, and your great questions. Have a good rest of the day.
Speaker #4: But continue to think, becoming there, good position we have, I done China, position in a remain disciplined, because there's—when for deals and competition, the prices, price are going up.
Speaker #4: And of prices and . focused stay on what we're doing . we have stop some , some , leverage our us have to be on some of the road show .
Speaker #4: And of prices and . focused stay on what we're doing . we have stop some , some , leverage our us have to be on some of the road yes , So thank you here for all your We can interest and so much questions .