AstraZeneca PLC

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 harbour statement. The company intends to utilise the safe harbour provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements with respect to the operations and financial performance of AstraZeneca. Although we believe our expectations are based on reasonable assumptions, by their very nature, forward-looking statements involve risks and uncertainties. and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these forward-looking statements. Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements. Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this 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. And 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 organisation. I must advise you that this presentation is being recorded today. And with that, I will now hand you over to the company.

Right, a warm welcome everybody to AstraZeneca's full year at fourth quarter 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. 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 harbour 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. 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. Next slide please. Here's the agenda for today's call. Following our prepared 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 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.

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 innovative medicines. Our core EPS, as you can see here, grew by 11%. We had 16 blockbuster medicines in 2025 with 17 medicines 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. 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 2025. At our full year results last year, we signalled that we are entering an unprecedented catalyst-rich period for our company. Our R&D teams continue to deliver. We had 16 positive Phase 3 trial redoubts in 2025. Together, they have a combined PQR sales potential of 10 billion, as you see on this slide. In the last 12 months, we have secured 43 approvals for 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. It's for the company to do this in particular work. 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. So if we move to the next slide, the strengths of our portfolio was clear in 2025. And we are not 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. Why don't you keep in mind, I know a couple of years ago, many questions we were getting were, your pipeline is complicated, it's 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, makes you very profitable and makes you look good. But one of those, 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 RNA in particular, growing each 17% and 12% respectively. CVRM, of course, was impacted by the panel expiry of Brelinta and Farciga in the UK, and there will be more of this, unfortunately, in 2026. Despite this, we still grow 2%. And overall, biopharmaceuticals still grow 6% and represent about 40% of our global sales. Rare disease grew 5%, despite the impact of biosimilars on solaris. I'd say the transition from solaris to ultramaris is not totally finished, but close to being completed. And ultramaris 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 Pulmicor 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. As I said, Europe will 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 3 trials, it's an enormous momentum going through the pipeline, and this year we should have 20 phase 3 readouts. And those readouts, fingers crossed, of course, if they are positive, they will collectively drive 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 3 readouts need to be positive. Importantly, you can see that there is a growing number of let's stage 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 PQR 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. So the question is often asked of us beyond 2030, and we said back in May 2024, and we continue saying the same, we want to be a gross company until 2030, reach this 80 billion ambition, but also be a gross company post-2030. And 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. So you can see here the list of the five... technologies that we prioritized and decided to invest in. And if you look at weight management, cardiovascular risk factors, we now have two products in phase three. Of course, our all PCSK9, for which we will get data in 2027. But we also announced that we have moved our oral GLIP1 into phase 3, 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 GLIP1. 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. So we are waiting for data on our GLIP1 glucagon and our amylin product. The GLIP1 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 Eight ADCs that are ADCs that came out of our own pipeline, our own efforts. Three of those are in phase three. We will get data in the first half of this year for one of those, as you can see here at Senevi. 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 payloads ADC. We have radio ligands. So we continue to build this. That will drive our growth post-2030. We, of course, invest in our next generation IOBA specifics, in particular, Rilve-Gostomig. 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 three. And on top of this, we have multiple approaches to CAR-T, not only CAR-T, but also allergenic projects, and 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. And finally, we're making progress also in our gene therapy programs. So if we move to the next one, I'll hand it out to Hannah, who will take you through the final shows. Thank you.

Thank you, Pascal, and good afternoon, everyone, and good morning to our colleagues in the U.S. 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 NHER2, Tespire, and Befortis 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 Sofnello and Wilbur Gostomig, which were recorded in the cost of sales. 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 3. SG&A expenses increased by only 3% in 2025. reflecting continued cost discipline and focus on operating leverage. We continue to streamline our business, and 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 rates 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. 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 investments to increase by approximately one-third versus 2025 as we expand capacity to support future growth. This includes our recently announced U.S. 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 ESL Biotech. 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. 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, 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 Forsiga, Limparza, and Roxidustat. Forsiga will also face loss of exclusivity in the U.S. in April. In 2025, U.S. Farsiga 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 Farsiga 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 percentage at constant exchange rates. 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 percentage range of total revenue in 2026. SG&A as a 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 Baxterstat, Camisestrant, and Garfilumab, all of which are medicines with blockbuster potential. 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.

Thank you, Radna. 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 Lumparza sales milestone. Many of our key medicines have surpassed notable multi-blockbuster milestones, with Tigrisso achieving over $7 billion in full-year revenues, Infinzi over $6 billion, Calquence over $3.5 billion, and Inheritu 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 Lumparza milestone, with all our key medicines in regions demonstrating double-digit growth. Tegresso 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 Flora 2 being the clear preference across key markets. In earlier lines, increased adoption of Adora and LoRa has been another meaningful source of growth. Infinzi 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. CalQuint's total revenues increased 17% in the fourth quarter driven by additional demand in frontline CLL as we maintain our class leadership position across major markets. 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. In HER2 delivered total revenue growth of 46% in the fourth quarter. Across all regions, in HER2 is seeing share gains both in HER2 positive and HER2 low metastatic breast cancer. And in China, demand continues to increase following NRDL enlistment in January of last year. TrueCap revenues grew 41% in the fourth quarter, with year-over-year comparisons benefiting from both inventory build in the U.S. and the reversal of pricing accruals in Europe. In the U.S., we now believe TrueCap is at peak, with further incremental growth to be driven by other markets. Finally, Datchaway revenues of $40 million in the fourth quarter reflect our early launch momentum in late-line EGFR-mutated lung cancer, including an emerging leadership position in the third line. Next slide, please. The strong momentum in 2025 continues into 2026. For Infinzi, we were pleased to see the U.S. 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 Infinzi combinations, including M. judo in bladder cancer and HCC, and with Datraway in lung, with commercial launches planned in 2027, pending, of course, positive results and regulatory approvals. 2026 is set to be another landmark year for HER2 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. This includes the first-line metastatic setting following the recent approval of Destiny Breast 09, with approvals in early breast cancer for Destiny Breast 11 and DB05 also expected this year. Looking to 2027 and beyond, we remain focused on bringing in HER2 to more patients globally, including in settings beyond breast cancer, such as lung cancer. For Calquence, we expect the imminent U.S. launch of the Amplify finite 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. Building on double-digit growth for Tegresso in 2025, we anticipate strong performance in 2026, driven by further adoption and geographic expansion of LoRa and Adora 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 TIGRISO as the backbone TKI, both in later lines with Saffron and Tropion Lung 15, and in the front line with Tropion Lung 14. 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.

Thank you, Dave. So, momentum continues to build across our oncology portfolio, and 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, Dattaway. Last year, we saw Dattaway 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. Tropium Bresto 2 has now been accepted by the FDA for priority review. This year, we expect the readout for Avanzar, a pivotal trial evaluating Daturae as the first-line lung cancer setting. Avanzar investigates the combination of Daturae with Infimzee and carboplatin, aiming to deepen and extend responses for this large, high unmet need population. Crucially, Avanzar will be the first trial to validate our QCS TROP2 NMR biomarker, designed to identify patients most likely to respond to Daturae in this first-line lung cancer setting. Success here could enable broader application of this technology in other tumour types and across our ADC portfolio. Building on Daturae's current approval and later-line EGFR-mutated lung cancer, we also anticipate the readout from Tropion Lung 15, which evaluates Daturae alone or in combination with Tegresso for patients who have progressed on a TKI. This trial aims to set new standards for second-line treatment, further reinforcing Degrisso's role as the backbone of care in EGFR mutant lung cancer and paving the way for tropion lung 14 in first-line setting, which can build on the success of FLORA and FLORA2. Infimsy continues to deliver transformative benefits across cancer types, and this year's key readouts in GI, lung, and bladder cancers signal a third wave of infimsy growth, highlighting the potential of combination regimens. I want to highlight two today. Firstly, the Emerald 3 trial aims to bring the combination of Infimsi and Indudo 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 Infimzee as the first perioperative immunotherapy regimen in cisplatin-eligible patients. Volga explores whether the combination of infortimab-vidotin and Infimzee plus or minus Imdudo can improve outcomes for the 50% of patients that are not candidates for cisplatin. This regimen is differentiated in two important ways. First, infortimab-vidotin is limited to the neoadjuvant setting. aiming to optimize outcomes while balancing the overall benefit-risk profile. And secondly, acknowledging bladder cancer's sensitivity to CTLA-4 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 camisestrant, our next-generation oral SIRD. Last year, we shared the first phase 3 data for camisestrant in patients with first-line hormone receptor positive disease with emerging ESR1 mutations. The transformational Serena 6 results demonstrated that intervening at the earliest opportunity and switching to a more effective endocrine option ahead of progression with camisestrant and the switching with camisestrant offers the chance to retain control of a patient's disease for longer and thereby realises the full potential of first-line treatment. In the second half of this year, Serena 4 will read out, targeting a broader upfront first-line population eligible for the combination of a CDK4-6 inhibitor and an aromatase inhibitor, and assessing whether camazestrin can replace the aromatase inhibitor to improve outcomes. Our confidence is driven not only by our data from the Phase 2 Serena 2 and the Phase 3 Serena 6 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 Sunny V, according to 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 And 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.

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 gross medicines substantially outpacing the impact of generic entry on a limited number of brands, such as Berlinda in the United States and Europe, and Forsiga in the United Kingdom. In the fourth quarter, R&I revenues were up by 10%, with revenue from gross medicines having increased by 27%. CVRM revenues were 6% down on the prior year, with generic competition slowing Fasica's growth to 2% and Belinta continuing to decline. VNI total revenue was down 33% year-on-year, largely due to the Bay Fortis sales milestone booked in the fourth quarter of 2024. Next slide, please. Biologic medicines continue to gain share among severe asthma patients. 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 Fasandra'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. Tesfai 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 Tespire 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. Breastfree is the fastest growing medicine within the expanding OPD. 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 LOCOS trials, and we anticipate first approvals in the first half of 2026. Savnello, a biological medicine for the treatment of SLE, is continuing to grow strongly, with the IV formulation having gained market leadership in several major markets. Savnello'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 Savnello 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 Localma's strong growth to continue into 2026 driven by market leadership within the growing potassium binder class. We have also increased additional manufacturing capacity to support our growth ambitions. In 2026, as mentioned, we anticipate FASIGA VBP implementation in China during the first quarter and the first generic competition in the United States in April. While FASIGA 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 3 development, with the first two phase 3 trials due to readout in 2027. We are currently preparing for the launch of Bexostat, an uncontrolled and treatment-resistant hypertension. The US approval is anticipated to broadly coincide with the entry of generic dapagliflozin in this market, allowing us to leverage our existing commercial infrastructure. While Bexostat 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 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 Wenhua and ATTR cardiomyopathy, which represents a major potential growth driver for the biopharmaceuticals business.

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 CVRM and RNI. 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 Wynua. We expect the CardioTransform readout in ATTR cardiomyopathy in the second half of this year. Wynua is an antisense oligonucleotide designed selectively to suppress hepatic production of transthyretin, addressing the upstream driver of amyloid fibro formation. ATTR cardiomyopathy 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. CardioTransform is the largest study ever conducted in this disease, enrolling more than 1,400 patients to receive Wynua 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, Wynua 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. Wynua 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 Wynua in combination with our depleter, Clarametug, in the near future. Turning now to the Phase III program for our differentiated IL-33 biologic, toziracumab in COPD, which we anticipate will read out 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 toziracumab. Should the results be positive, toziracumab 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. We are delighted to announce today that our once daily oral GLP-1 receptor agonist, Alecoglipron, 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 Alekoglipron 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. Our diversified pipeline uniquely positions us to explore innovative, novel combinations, and alongside Alecoglipron, we continue to advance our broader portfolio of different mechanisms, including a selective amylin receptor agonist, AZD6234, and 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. And with that, please proceed to the next slide, and I'll pass over to Mark to cover rare disease.

Thank you Sharon, and can I get to the next slide please? Rare disease delivered total revenue of $9.1 billion in 2025, up 4% over last year, driven by growth in neurology indications, increased patient demand, and continued global expansion. In the quarter, ultramarine grew 15%, driven by patient demand across indications, including the competitive GMG and P&H markets. Soliris revenues continue to decline due to the successful conversion to eutomeris, as well as biosimilar pressure. Strensic grew 15% due to strong demand, with the quarter benefiting from tender order timing. We also saw strong underlying demand for Cosellugo offset in the fourth quarter, by all the timing in certain tender markets. We continue to see great momentum across the rare disease portfolio, with further approvals for Koselugo and Ultomeris, expanding our geographic reach for these medicines. 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, Alexio 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 Ericsson 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 and enable the seamless extent of technologies and advancements across medicinal and process chemistry, molecular editing and library platform. 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 career. Please advance to the next slide. In 2026, we expect Eltomiris to continue to grow driven primarily by neurology indication, including new-to-brand patients and those switching from Soliris, as well as further market expansions. We indicated picture sales for Eltomiris to be above $5 billion, with contributions from both existing and new indications, such as HCT-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 HCT-TMA. This data builds on the positive findings from the single-arm pediatric study completed in 2025. For strain-sick, 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 S-infotase-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 COSELU-GOS 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. Our antibody-based depletion portfolio for cardiac and systemic amyloidosis continue to advance, with a focus on the two most prevalent forms of amyloidosis, transthyretin and light chain. We announced the first phase 3 result last year for our most advanced pipeline candidate, Oncelamimab. In the CARES phase 3 program, Oncelamimab demonstrated a highly clinically meaningful improvement in both all-cause mortality and cardiovascular spasticization in the subgroup of patients with kappa light chain amyloidosis. Global regulatory reviews and submissions are underway. We have also expanded our collaboration with Norimune in December 25 to include NI-009, a fibril depleting antibody for the lambda light-chain amyloidosis, which represents 80% of the light-chain population, and complements onselamimab to address the broad patient population. We have accelerated development plans to move this molecule as quickly as possible into the clinic. Clearamitug, our first collaboration with NeurImmune, is now in phase 3 for ATTR cardiomyopathy. The depleter 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 2B of our silencer Wenua with our depleter Clearamitug, and we believe the combination of these two medicines has the potential to deliver a new standard of care for patients with ATTR cardiomyopathy. The data generation to date reinforce a belief that targeted amyloid febrile depletion with specific antibodies can significantly reduce mortality and hospitalization, transforming the course of the disease for this patient. And with that, please add on 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. We have a significant number of high-value, face-free trials that can redirect and support our growth to 2030 and beyond. And in 2026 alone, the risk-adjusted combined PKR 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 in 2025, and our confidence in delivering the 80 billion ambition by 2030 is definitely increasing. With our broad portfolio and 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 post-2030. We'll 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. 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 humour, 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 Yoris, who must be somewhere in the room. Okay, welcome Yoris. Yoris was until recently the country president for the U.S. biopharma and overall president, representative of ESEA in the United States. And Joris has driven tremendous growth throughout our company in the United States. In particular, built Fasiga to what it is, Fasenra, Tespire, and really done a great job. Joris, before being in the U.S., worked in Asia. And so he has really great experience across Asia, the U.S., and Europe since he joined the company in 2000. So I'm sure Yoris will also do a great job in IR, and I'm sure you'll enjoy working with him. So if 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.

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. 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.

Thank you. Ishkhad, 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, Ishkhad, to start.

Thank you 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.

Can you speak in a microphone?

I don't know whether it works. Is it better now? it definitely gives the confidence in the outlook of 26. Now, when you think about 26 in China, I think there are two main components. One is, obviously, the headwind of the VVP for SIGA, Roksodustat, and Limparza. And as we have always seen, there is a... expectations of the decline post-VVP that is driven by both price decreases as well as volume reduction. But when it comes specifically to ForSiga, I do believe that we can also expect the brand recovery in the mid-term, and we saw the similar trend with Betalock and Crestor in the past. And it is really driven by the, you know, strong brand perception, strong brand loyalty, and the recovery specifically in the retail channel. 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 Fasendra, TrueCup, and Calfred's tablets in the NRDL starting 1st of January this year. When you think about in here to performance for standard DLN, Dave mentioned that in his presentation, we saw very strong uptake and our ability to include and here to in the more than 1,000 hospital listings in the less than a quarter gives us a confidence that we will be able to see the successful logics going forward. When it comes to the profitability, profitability in China is still lower than the group, but I think you always need to think about the huge volume and huge unmet need and opportunity there and put that in the perspective of the a bit lower prices than in the rest of the world.

In your first question, I had like 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 for 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 Stanford and using AI and multimodal model to actually help improve the probability of success in our studies and better shape them. 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 and hematology?

Yeah, thanks, Pascal. So, you know, 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 Limpaza. It's been important with Tigris. So 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, cancer data where available, imaging and pathology, and integrate all of that into the largest foundation model for oncology because of the large data set that we have with Tempus and Pathos. The hope is, I mean, what we've already been doing is using those kinds of real-world evidence data sets to both help design our phase three 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 3 trials by using these foundation models. The hope is also that you could better identify the patient population's 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. 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.

Dave, do you want to cover the second part? Yeah, just on the second. And then, Ruth, if you could also talk about a couple of products in BioPharm that would drive growths.

So, Louisa, very specifically on the readouts that Pascal went through, Emerald III is a blockbuster-plus opportunity in HCC and I think builds off of a program that has currently success within FinSEE. 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 4 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.

Yeah, and a few highlights from a biopharma perspective. Lara Profstad, our oral PCSK9, we're going to expect the first data set in the course of 2027. is, in our view, a very high potential, potentially a $5 billion-plus potential. Clearly, Baxrostat. I'm sure there are many more questions about Baxrostat. Not only the mono component, but also the combination, I think, with the SDLT2, dapagriflozin, is a very important one. And then the other two combinations, DALCI and DAPA, in kidney disease and heart failure, is a potential where there's a high medical needs. And the combination of zebutantin 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 Tozo. Tozo, as mentioned by Sharon, is a high medical need still in the COPD space. 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.

Yeah, thanks Pascal. Richard Vosser from JP Morgan. Maybe thoughts on the implications of the LIDEA result over to the Serena 4 trial in terms of design. Susan, you mentioned choosing the right patient population. thoughts on what you've done in Serena 4 on the back of the Lideria result. Maybe if I can sneak it, thoughts on Cambria 1 as well, given what Lideria, does that impact the commerciality? But Pascal, ignore that if that is too.

And I will grant you the second one, because it's still related to Cambria anyway. So over to you, Susan.

So, I mean, I think what we've now seen is proof, as we've been saying consistently, that CERD's 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, but in the endocrine-sensitive ESR wild type. 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. At least 12 months must have elapsed since the patient's last dose of the adjuvant AI. And then there's some patients with de novo stage four 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, it is still those trial design features, and of course, it's in combination with the CDK4-6 inhibitor. So your second question about Cambria One, again, I would just point out that we're the only company that has two adjuvant studies with our CERD, one designed for the patient population after two to five years. from the patient population newly diagnosed, which is Cambria 2. That gives us the opportunity to be able, 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 a Bermacycline, 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 and we're optimistic that those trials will read out positive given people's principle, if you like, that this class can have a difference there.

We've just finished this table.

I think I've got the mic, Pascal, if I can. It's Matthew Weston from UBS. One question, please, on Aleka Glipron, if I can. You've made the announcement that you're moving to phase three, which I assume indicates confidence in the phase two 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 three, 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 three 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?

Let me just answer this one because it's easy to answer. We would never move a product in Phase 3 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 three and unlock so much investment. Maybe James?

Thanks a lot. James from Barclays. One of the phase three readouts in the first half is azimutase alpha, which I think had been badged as a three to five billion opportunity. I'm aware there's three different trials, so is it a all or nothing to get the three to five billion, or are there scenarios where some trials are more or less successful, and how would that break down?

Yeah, so thank you for asking the question there. As you are mentioning, there are three trials. There are two trials in the pediatric population where StremCyc was originally approved. One of these trials is a switch from StremCyc to a shinspotase. There is another trial in the pediatric population in the naive, in the strength sick naive population against placebo. And the third trial combines both adolescent and adult. You know that the level of strength sick, depending on the jurisdiction, is usually focusing on the pediatric population. And sometimes we have, you know, adults with pediatric onset in the label. But the intent of the esphinxotase program was to test in the totality of the population from pediatric adolescent onset. adult and even adult of a certain age, if I may say. 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 StrainSeq. 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 Stensic, 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 Esfinsvater Alpha a product several times the value of Stensic.

Thank you. It's Mike Leuchten from Jefferies. I think this is for Dave and Susan. Tropian Lung 07 now has QCS in the protocol. Is that also the plan for Tropian Lung 08? And can you talk about the relative importance of Avanza versus TLO 07, TLO 08?

Can we start first? Okay, thanks for the question. So, you know, tropion lung O8 is only in the PD-L1 greater than 50% patient population, which is a smaller segment overall. So if you just look at the trial characteristics, it makes sense. for the biomarker to be applied within the TLO7 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 TLO7, we'll be answering the question about the added benefit of TLO7 platinum in addition as well you know and I think these are all important trials that have the opportunity to really position dataway as a key component of the first line setting across multiple segments of that patient population

Thanks, Graham Perry from Citi. So it's another question, follow-up to Richard's question on cambridestrin in the adjuvant setting. So Cambria 1 is looking at essentially a switch from aromatase inhibitors, but the giridestrin LIDERA study suggests that perhaps that market opportunity might be quite small over time if giridestrin becomes standard of care in naive 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 Virginia? Thanks.

So just to go over again, the Cambria 2 studies in a setting that's very similar to Ladera, but it does allow for the combination with Abema cyclic, which I think is going to become an increasing piece. Of course, what Ladera doesn't answer is the relevance of the oral SIRD 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, you want to comment?

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 1, which is in this two- to five-year population, that's the prevalent population. And so while it's true that over time the upfront Cambria 2 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 combination. 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.

Thanks, Dave. Can we go here and then maybe there?

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 tozolacumab, both in terms of the molecule and trial design, and how that underpins your confidence in the program? Thanks so much.

Sure, and thanks for the question. So the story about toziracumab 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 toziracumab In current and former smokers, 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.

Can we time one more question in the room, and then we'll take Steve's question online.

Thanks.

Can we get a microphone over there?

Yeah, go ahead. Christopher from SCB. Thanks for taking my question. It's on Calquins and the room for growth. It's done a nice job beating again lately. Consensus has about 10%, give or take 5%. growth for 26 or 25, then another 10% from then to about 2031, so it peaks at 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?

So thanks, Chris, for the question. Amplify is very much an important part of the growth moving forward for CalQuest and the fact that we've got positive study approval within Europe and we're anticipating the U.S. 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, and 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 U.S., remember that there is not a BCL-2 and a BTKI combination finite CLL approach that's been approved. So we have an opportunity in the U.S. to really be the first to come into this space. And one in two patients are receiving finite as opposed to treatment progression in the U.S. So you can see how getting to growth numbers within the U.S., which is certainly the largest portion of our global CalQuint 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 will read out a little bit later on.

Go ahead. We need a microphone. Yeah, go ahead.

Justin Smith from Bernstein. Sharon, one for you if that's okay. Cardio transforms. 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?

Right, so this question comes up a lot with Wynua, and I think it really speaks to the interest in novel therapeutics for patients living with ATTR cardiomyopathy, 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 pre-planned subgroup analyses. One of those is to be able to differentiate between patients on baseline tefamidus versus those who are not. And our trial will have the largest proportion and number of patients who are on baseline tefamidus. 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. 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.

Thanks, Sharon. So we'll take Steve Scott's question online and then return to the room. I think Rajan has the microphone. So Steve, over to you.

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 increasing 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.

I will only take the first one, if I may. It's an easy one, I'll vote for you.

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 oral's moving in, but there's still so much improvement possible and combination therapies for obesity, overweighted people, I think is 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 FASEGA, a big part of the success of FASEGA across the three indications is that we have a very large footprint in the international markets. So there's clearly room to maneuver. 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. 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.

Thank you.

Thanks for taking my question. It's Rajen 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 FARC-SEGA LOE? And then just thinking about the guidance for 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?

Yeah, so let me take that question as a start. First of all, I think the respiratory 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 Dress Free, potentials with asthma, what I said in my pre-travel remarks, products like Tespire, Fasanra, are not growing any more 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 BaxterStat in the course of this year as an approval. That, of course, will not immediately generate substantial sales in the course of 2026. It's a highly dominated 5D population, 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 FASEGA 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.

Hi, Rajesh Kumar from HSBC. 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 lists 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. So how are you thinking about that problem in terms of reallocation of capital, share buyback or future investments?

So let me make a general comment and then Radna can make more specific comments about capital allocation. One thing I would add to what Ruth said about, or Lipwan and others is, carbon metabolism 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 GLIP1, you know, you also have SGLT2. And I really believe in the oral segment. Combining those two is going to make a huge difference to how people are treated. I think the foundation treatment of many of these people should be GLIP1 and SGLT2. Protect the kidneys, the heart, reduce weight, improve metabolic status. And then, you know, beyond that, we have other mechanisms, of course. So I think this is going to remain... I mean, it is looking very crowded, 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 the R&D 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 will become profitable as soon as we can get to scale. In terms of general question about capital allocation,

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, you know, we're very comfortable at 1.2 times 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, you know, it's not about just buying assets. It's about actually creating value for shareholders from those assets that we acquire. And that requires, you know, substantial investments in R&D once we acquire those assets or license those assets, et cetera. Again, we are very disciplined in how we do that and we need to continue to add value 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 won't say, you know, 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, you know, continue the growth race because we know in that time frame there are going to be substantial LOEs.

If you look at it, I mean, we are in... in a good position. We don't have to go after face-to-face assets that are proven and cost a fortune and you pay up front what you're going to get later. We really try to focus our BD activities on earlier assets where we can add value and create earlier value. Because, you know, 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 BD 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, 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.

There's one online.

Sorry, online. That's what you mean. Sorry. Peter, I'd be in fear. Over to you, Peter Verdult.

Thanks, Pascal. Peter Knott here from BNP. Sorry I can't be with you live. Just two quick ones, please. Susan and Sharon. For Susan on Arteogen, 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 front of persons of 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 silencer data in the market? So put simply, do you think you can raise the bar further on outcomes in the silencer market? Thank you.

Can we focus on the first question and if we have time we will return to the second one later?

Yes. 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 infinity to look at. But also, we have the opportunity to look at subcutaneous formulations also with our ADC portfolio portfolio. you know, which is perhaps slightly more surprising to people, but it is possible to do that in certain circumstances. And then, of course, you know, across our T cell engagers, the actual doses in the T cell engager portfolio are often low enough that 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 biologics part of the portfolio.

And Sian?

Sian? Sure. So going back to CardioTransform for a planterson, 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 defamative 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 acrimonious 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. 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.

So maybe we take the last one. Mathias Legbraum at Anders Banken is online. Over to you, Mathias.

Thank you very much. I'm curious to hear how you think about AstraZeneca's competitive advantage from an in-license or M&A point of view, given you have two signed sites in China, when competing for assets with a competitor who does not have R&D on-site in China.

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 BD viewpoint. If that's the question, let me try. You know, 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 centres, we have a strong position, strong profile in China A few of the deals we've made, we were able to make because people wanted to work with us. The recent deal we made, I know that someone else wanted to pay more money, but the company wanted to work with us. 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 bitty deals is going up, right? And that's, I assume that would be the case and that's why after COVID-19 And when the country reopened, we quickly went down. We've done quite a number of deals over the last few years at reasonable prices 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 your interest and your great questions. Have a good rest of the day.